By venynx, 2019-10-18
Hydrochlorothiazide - Clinical Pharmacology
The mechanism of the antihypertensive effect of thiazides is unknown.Hydrochlorothiazide powder does not usually affect normal blood pressure.
Hydrochlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosage all thiazides are approximately equal in their diuretic efficacy.Hydrochlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate.After oral use diuresis begins within 2 hours, peaks in about 4 hours and lasts about 6 to 12 hours.
Pharmacokinetics and Metabolism
Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. When plasma levels have been followed for at least 24 hours, the plasma half-life has been observed to vary between 5.6 and 14.8 hours. At least 61 percent of the oral dose is eliminated unchanged within 24 hours. Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
Indications and Usage for Hydrochlorothiazide
Hydrochlorothiazide tablets, USP are indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy.Hydrochlorothiazide tablets, USP have also been found useful in edema due to various forms of renal dysfunction such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure.
Hydrochlorothiazide tablets, USP are indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension.
Use in Pregnancy
Routine use of diuretics during normal pregnancy is inappropriate and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy and there is no satisfactory evidence that they are useful in the treatment of toxemia.
Edema during pregnancy may arise from pathologic causes or from the physiologic and mechanical consequences of pregnancy. Thiazides are indicated in pregnancy when edema is due to pathologic causes, just as they are in the absence of pregnancy (see PRECAUTIONS, Pregnancy). Dependent edema in pregnancy, resulting from restriction of venous return by the gravid uterus, is properly treated through elevation of the lower extremities and use of support stockings. Use of diuretics to lower intravascular volume in this instance is illogical and unnecessary. During normal pregnancy there is hypervolemia which is not harmful to the fetus or the mother in the absence of cardiovascular disease. However, it may be associated with edema, rarely generalized edema. If such edema causes discomfort, increased recumbency will often provide relief. Rarely this edema may cause extreme discomfort which is not relieved by rest. In these instances, a short course of diuretic therapy may provide relief and be appropriate.
By venynx, 2019-10-18
Furosemide Injection - Clinical Pharmacology
Investigations into the mode of action of furosemide have utilized micropuncture studies is rats, stop flow experiments in dogs and various clearance studies in both humans and experimental animals. It has been demonstrated that furosemide inhibits primarily the reabsorption of sodium and chloride not only in the proximal and distal tubules but also in the loop of Henle. The high degree of efficacy is largely due to this unique site of action. The action on the distal tubule is independent of any inhibitory effect on carbonic anhydrase and aldosterone.Furosemide powder
Recent evidence suggests that furosemide glucuronide is the only or at least the major biotransformation product of furosemide in man. Furosemide is extensively bound to plasma proteins, mainly to albumin. Plasma concentrations ranging from 1 to 400 μg/mL are 91 to 99% bound in healthy individuals. The unbound fraction averages 2.3 to 4.1% at therapeutic concentrations.
The onset of diuresis following intravenous administration is within 5 minutes and somewhat later after intramuscular administration. The peak effect occurs within the first half hour. The duration of diuretic effect is approximately 2 hours.
In fasted normal men, the mean bioavailability of furosemide from furosemide tablets and furosemide oral solution is 64 % and 60%, respectively, of that from an intravenous injection of the drug. Although furosemide is more rapidly absorbed from the oral solution (50 minutes) than from the tablet (87 minutes), peak plasma levels and area under the plasma concentration-time curves do not differ significantly. Peak plasma concentrations increase with increasing dose but times-to-peak do not differ among doses. The terminal half-life of furosemide is approximately 2 hours.
Significantly more furosemide is excreted in urine following the intravenous injection than after the tablet or oral solution. There are no significant differences between the two oral formulations in the amount of unchanged drug excreted in urine.
Furosemide binding to albumin may be reduced in elderly patients. Furosemide is predominantly excreted unchanged in the urine. The renal clearance of furosemide after intravenous administration in older healthy male subjects (60-70 years of age) is statistically significantly smaller than in younger healthy male subjects (20-35 years of age). The intial diuretic effect of furosemide in older subjects is decreased relative to younger subjects. (See PRECAUTIONS: Geriatric Use.)
Parenteral therapy should be reserved for patients unable to take oral medication or for patients in emergency clinical situations.
Edema: Furosemide is indicated in adults and pediatric patients for the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. Furosemide is particularly useful when an agent with greater diuretic potential is desired.
Furosemide is indicated as adjunctive therapy in acute pulmonary edema. The intravenous administration of furosemide is indicated when a rapid onset of diuresis is desired, e.g., in acute pulmonary edema.
If gastrointestinal absorption is impaired or oral medication is not practical for any reason, furosemide is indicated by the intravenous or intramuscular route. Parenteral use should be replaced with oral furosemide as soon as practical.
By venynx, 2019-10-18
Budesonide and formoterol (eformoterol) fumarate dihydrate powder
This leaflet answers some common questions about DuoResp Spiromax. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.Formoterol
All medicines have benefits and risks. Your doctor has weighed the risks of you using DuoResp Spiromax against the benefits they expect it will have for you.DuoResp Spiromax is inhaled into the lungs for the treatment of asthma or Chronic Obstructive Pulmonary Disease (COPD).
DuoResp Spiromax contains two active ingredients in one inhaler: budesonide and formoterol (eformoterol) fumarate dihydrate (hereafter referred to as formoterol).
Budesonide belongs to a group of medicines called corticosteroids. Budesonide acts directly on your airways to reduce inflammation.
Formoterol belongs to a group of medicines called beta-2-agonists. Formoterol opens up the airways to help you breathe more easily.
Asthma is a disease where the airways of the lungs become narrow and inflamed (swollen), making it difficult to breathe. This may be due to an allergy to house dust mites, smoke, air pollution or other things that irritate your lungs.
DuoResp Spiromax contains budesonide and formoterol in one inhaler.
Budesonide helps to improve your condition and to prevent asthma attacks from occurring. It is a "preventer" and needs to be taken regularly.
Formoterol helps you breathe more easily. It should also be taken regularly to help control your symptoms.
Budesonide and formoterol in combination, when used regularly, will help prevent asthma attacks and make it easier to breathe normally.
DuoResp Spiromax can also be used as a "reliever" when needed to treat your symptoms when your asthma gets worse and when used regularly will help prevent asthma attacks.COPD (which includes chronic bronchitis and emphysema) is a long-term lung disease. There is often permanent narrowing and persistent inflammation of the airways.
Symptoms may include difficulty in breathing (breathlessness or wheezing), coughing and increased sputum.
When used as prescribed, DuoResp Spiromax will help to control your COPD symptoms (i.e. breathing difficulties)
By venynx, 2019-10-18
Formoterol Fumarate Capsule
Formoterol powder is a long-acting bronchodilator used as a long-term (maintenance) treatment to prevent or decrease wheezing and trouble breathing caused by asthma or ongoing lung disease (chronic obstructive pulmonary disease-COPD, which includes chronic bronchitis and emphysema). It should only be used long-term if your asthma symptoms are not controlled by your other asthma medications (such as inhaled corticosteroids). Formoterol must not be used alone to treat asthma. (See also Warning section.) It works in the airways by relaxing muscles and opening air passages to improve breathing. Controlling symptoms of breathing problems can decrease time lost from work or school.
This drug is also used to prevent breathing difficulties brought on by exercise (exercise-induced bronchospasm-EIB).This medication should not be used for a severe/sudden asthma attack. For sudden attacks of asthma, use your quick-relief inhaler as prescribed. This medication is not a substitute for inhaled or oral corticosteroids (e.g., beclomethasone, fluticasone, prednisone). This medication should be used along with another controller-type asthma medication (such as inhaled corticosteroids). However, it should not be used with other long-acting beta-agonist inhalers (such as arformoterol, salmeterol) because doing so may increase your risk for side effects.
It is recommended that children and teenagers, who need to use formoterol to treat their asthma, should use a combination formoterol/budesonide product. Check with your child's doctor to see if this product is the right product for your child.How to use Formoterol Fumarate Capsule, With Inhalation Device.Learn the proper use of formoterol, and carefully read the Medication Guide that comes with the product. Consult your pharmacist for more details.
Formoterol comes in a capsule. Do not swallow these capsules by mouth. Inhale the contents of the capsule by mouth using the inhaler device, usually one capsule twice daily (morning and evening) or as directed by your doctor. The two doses should be about 12 hours apart. Formoterol must always be used with its own special inhaler device. Use the new inhaler device that you get each time you refill your formoterol prescription. Always discard your old inhaler device. Do not use a "spacer" device with the inhaler.
Leave the capsule sealed in the foil packet until just before use. Wash and completely dry hands before touching the capsules. Be sure to inhale rapidly and deeply through the mouthpiece when using this drug. Open the inhaler after use. Check that the capsule is empty. If it is not empty, close the inhaler and repeat. Do not exhale into the inhaler.
If you are using this medication to prevent exercise-induced breathing problems (EIB), it should be used at least 15 minutes before exercising. Do not use any more doses of formoterol for the next 12 hours. If you are already using formoterol twice daily, do not use any more doses for EIB.Your asthma must be stable (not worsening) before you start treatment with formoterol. Consult your doctor for more details.If you are using other inhalers at the same time, wait at least 1 minute between the use of each medication.
Learn which of your inhalers you should use every day (controller drugs) and which you should use if your breathing suddenly worsens (quick-relief drugs). Ask your doctor ahead of time what you should do if you have new or worsening cough or shortness of breath, wheezing, increased sputum, worsening peak flow meter readings, waking up at night with trouble breathing, if you use your quick-relief inhaler more often (more than 2 days a week), or if your quick-relief inhaler does not seem to be working well. Learn when you can treat sudden breathing problems by yourself and when you must get medical help right away.
Using too much formoterol or using it too often may result in a decrease in drug effectiveness and an increase in serious side effects. Do not use more than the recommended dosage or take this drug more often than prescribed. Do not stop or decrease the dose of other asthma medications (e.g., inhaled corticosteroids such as beclomethasone) without your doctor's approval. If you are using short-acting bronchodilators on a regular schedule (such as every six hours), you should stop taking them while using this drug.
Seek immediate medical attention if you notice any of the following signs of worsening asthma: the usual doses of your asthma medications no longer control symptoms, your quick-relief inhaler is less effective, or you need to use the quick-relief inhaler more often than usual (e.g., more than 4 puffs per day or more than 1 inhaler every 8 weeks). Do not increase your dose of formoterol in this situation.When used for an extended period, this medication may not work as well and may require different dosing. Talk with your doctor right away if this medication stops working well.
By venynx, 2019-10-18
Ethacrynic acid is a "water pill" (diuretic) that works in your kidneys to increase the amount of urine you make. This helps your body get rid of extra water. This medication is used to decrease swelling (edema) caused by conditions such as cancer, congestive heart failure, liver disease, and kidney disease. This effect can help your kidneys work better and lessen symptoms such as trouble breathing and swelling in your ankles, feet, hands, or belly.Ethacrynic acid powder
This medication should not be used for infants.
How to use Ethacrynic Acid
Take this medication by mouth as directed by your doctor, usually once or twice a day after a meal. If you take this drug too close to bedtime, you may need to wake up to urinate. It is best to take this medication at least 4 hours before your bedtime. Consult your doctor or pharmacist if you have questions about your dosing schedule.
The dosage is based on your medical condition and response to treatment. To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. Your doctor will adjust your dose based on your medical condition, response to treatment, and lab tests (such as sodium, potassium, chloride levels). Some people may be directed to take this medication every other day or only when needed. Follow your doctor's directions carefully.
If your doctor has directed you to take this medication on a regular schedule, take it regularly to get the most benefit from it. To help you remember, take it at the same time(s) each day.
By venynx, 2019-10-18
Cyclofenil 200 mg equals how many ml
Learn how to convert milligrams (mg) to milliliters (ml) with this article and Let's say we want to work out how many ml there are in 45mg of it. It is also equal to 1 cubic centimeter, or about 15 minims. Milligrams and Milliliters are commonly used measurement units used around the world. Any unit of. ligands endoxifen and cyclofenil-endoxifen hybrids covalently linked to the ERβ is expressed in many tissues and is the predominant ER in required incubation period, cells were fixed in 1 mL ethanol and µL PBS .. mmol) was reacted with endoxifen derivative (1 eq., mg, mmol).Cyclofenil powder
found in urine and authors did not report any analytical figure of merit to the active principle ( mg per tablet) was purchased in local drugstores. to- charge ratio equals Da) followed by the formation of a second even mL min Cyclofenil originally presents weak fluorescence in solution and it was not detected. Certain advertising, labelling and packaging requirements may also be a consequence of millilitres or less. Basil oil CYCLOFENIL. Many approaches have been investigated to improve the selectivity of drugs The high affinity nonsteroidal ER ligand cyclofenil diphenol (F) [32,33] .. After the required incubation period, cells were fixed in 1 mL ethanol and .. mg, mmol) was reacted with endoxifen derivative (1 eq., mg, mmol).
(b) that contain more than % by weight of any substance having the . "mg" for milligram; and. "ml" for millilitre; and .. Croton Seed. Curare. Cyclofenil supplied is labelled to show a maximum dose of mg and a maximum . medicinal product is equivalent to % of hydrocortisone, calculated in. cyclofenil suggested similarity in their effectiveness. Side effects natives to breastfeeding exist may seek lactation suppression on personal or Oral bromocriptine mg twice daily for 14 days (n = 49) versus oral pyridoxine Therefore, mL of breast secretion was manually collected from each woman daily.
By venynx, 2019-10-18
Should I avoid certain foods while taking Bisoprolol Fumarate?
Bisoprolol fumarate and hydrochlorothiazide tablets are indicated for the treatment of hypertension. It combines two antihypertensive agents in a once-daily dosage: a synthetic beta1-selective (cardioselective) adrenoceptor blocking agent (bisoprolol fumarate) and a benzothiadiazine diuretic (hydrochlorothiazide).
Bisoprolol fumarate is chemically described as (±)-1-[4-[[2-(1-methylethoxy)ethoxy]methyl]phenoxy]-3-[(1-methylethyl)amino]-2-propanol(E)-2-butenedioate (2:1) (salt). It possesses an asymmetric carbon atom in its structure and is provided as a racemic mixture. The S(-) enantiomer is responsible for most of the beta-blocking activity. Its empirical formula is (C18H31NO4)2•C4H4O4 and it has a molecular weight of 766.97. Its structural formula is:Bisoprolol powder
Bisoprolol fumarate is a white crystalline powder, approximately equally hydrophilic and lipophilic, and readily soluble in water, methanol, ethanol, and chloroform.
Hydrochlorothiazide (HCTZ) is 6-Chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. It is a white, or practically white, practically odorless crystalline powder. It is slightly soluble in water, sparingly soluble in dilute sodium hydroxide solution, freely soluble in n-butylamine and dimethylformamide, sparingly soluble in methanol, and insoluble in ether, chloroform, and dilute mineral acids. Its empirical formula is C7H8ClN3O4S2 and it has a molecular weight of 297.73. Its structural formula is:
Inactive ingredients include Corn Starch, Dibasic Calcium Phosphate, Hypromellose, Magnesium Stearate, Microcrystalline Cellulose, Polyethylene Glycol, Polysorbate 80, and Titanium Dioxide. The 10 mg/6.25mg tablet also contains Colloidal Silicon Dioxide. The 5 mg/6.25 mg tablet also contains Colloidal Silicon Dioxide, and Red and Yellow Iron Oxide. The 2.5 mg/6.25 mg tablet also contains Crospovidone, Pregelatinized Starch, and Yellow Iron Oxide.
Bisoprolol fumarate and HCTZ have been used individually and in combination for the treatment of hypertension. The antihypertensive effects of these agents are additive; HCTZ 6.25 mg significantly increases the antihypertensive effect of bisoprolol fumarate. The incidence of hypokalemia with the bisoprolol fumarate and HCTZ 6.25 mg combination (B/H) is significantly lower than with HCTZ 25 mg. In clinical trials of bisoprolol fumarate and hydrochlorothiazide tablets, mean changes in serum potassium for patients treated with bisoprolol fumarate and hydrochlorothiazide tablets 2.5/6.25 mg, 5/6.25 mg or 10/6.25 mg or placebo were less than ± 0.1 mEq/L. Mean changes in serum potassium for patients treated with any dose of bisoprolol in combination with HCTZ 25 mg ranged from -0.1 to -0.3 mEq/L.
Bisoprolol fumarate is a beta1-selective (cardioselective) adrenoceptor blocking agent without significant membrane stabilizing or intrinsic sympathomimetic activities in its therapeutic dose range. At higher doses (≥ 20 mg) bisoprolol fumarate also inhibits beta2-adrenoreceptors located in bronchial and vascular musculature. To retain relative selectivity, it is important to use the lowest effective dose.
Hydrochlorothiazide is a benzothiadiazine diuretic. Thiazides affect renal tubular mechanisms of electrolyte reabsorption and increase excretion of sodium and chloride in approximately equivalent amounts. Natriuresis causes a secondary loss of potassium.
By venynx, 2019-10-18
Bumetanide Prevents Brain Trauma-Induced Depressive-Like Behavior
Brain trauma triggers a cascade of deleterious events leading to enhanced incidence of drug resistant epilepsies, depression, and cognitive dysfunctions. The underlying mechanisms leading to these alterations are poorly understood and treatment that attenuates those sequels are not available. Using controlled-cortical impact as an experimental model of brain trauma in adult mice, we found a strong suppressive effect of the sodium-potassium-chloride importer (NKCC1) specific antagonist bumetanide on the appearance of depressive-like behavior. We demonstrate that this alteration in behavior is associated with an impairment of post-traumatic secondary neurogenesis within the dentate gyrus of the hippocampus. The mechanism mediating the effect of bumetanide involves early transient changes in the expression of chloride regulatory proteins and qualitative changes in GABA(A) mediated transmission from hyperpolarizing to depolarizing after brain trauma. This work opens new perspectives in the early treatment of human post-traumatic induced depression. Our results strongly suggest that bumetanide might constitute an efficient prophylactic treatment to reduce neurological and psychiatric consequences of brain trauma.Bumetanide powder
Brain trauma is the main cause of disability all over the world with a very high prevalence in developed countries (Meyer et al., 2008; Bondi et al., 2015). According to the World Health Organization and the Centers for Disease Control and Prevention (Meyer et al., 2008), brain trauma classification is based on multiple factors such as altered neurological functions, brain area of interest and genetic variations. Altogether, these factors lead to highly individualized injuries. Sequels of trauma include low prevalence post-traumatic epilepsies (PTEs), with a severity and occurrence dependent on trauma severity (Kelly et al., 2015; Bragin et al., 2016), and cognitive dysfunctions and depression-like phenotypes are also commonly associated (Peeters et al., 2015; Perry et al., 2015; Stein et al., 2015). Following brain trauma, neuronal cell death occurs and more particularly within the neurons of the dentate gyrus of the hippocampus (Ren et al., 2015; Samuels et al., 2015), leading to hippocampal volume reduction (Samuels et al., 2015; Anacker and Hen, 2017). These observations could be related to changes in post-traumatic neurogenesis in the hippocampus. This has been proposed to be a useful marker of therapeutic treatment efficacy (Brandon and McKay, 2015; Alvarez et al., 2016).
In a wide range of neurological and psychiatric disorders, GABAergic signaling is affected through chloride homeostasis impairment triggered by a down regulation of the main neuronal-specific chloride and potassium extruder, KCC2, and up regulation of the chloride importer NKCC1, respectively (Medina et al., 2014). Similar changes in GABAergic transmission have been reported in a different model of brain trauma (Ben-Ari, 2017). This leads to depolarization and also an excitatory action of GABA that could perturb the generation of behaviorally relevant oscillations and integrative properties of brain networks (Rivera et al., 1999; Luscher et al., 2011; Kahle et al., 2013; Medina et al., 2014; Ben-Ari, 2017). These shifts have been observed notably in developmental disorders including autism spectrum disorders (ASDs) (Tyzio et al., 2014), stroke (Jaenisch et al., 2010; Xu et al., 2016) and epilepsy (Pallud et al., 2014; Tyzio et al., 2014; Kelley et al., 2016). The interaction between major depressive disorders (MDDs) and GABAergic neurotransmission has been suggested in a genetic mice model of GABA(B)-R knock-out (Mombereau et al., 2005) and in studies showing an antidepressant effect of potent and selective blockage of GABA(A) transmission (Rudolph and Knoflach, 2011) at both the hippocampus (Boldrini et al., 2013) and mesolimbic system (Kandratavicius et al., 2014). In addition, several observations link chloride homeostasis to secondary neurogenesis through GABA(A) neurotransmission (Luscher et al., 2011; Ostroumov et al., 2016). The generation of new neurons within the DG requires different steps: first, the transition from quiescent to proliferative progenitors, then their differentiation to immature neurons in a GABAergic-dependent manner (Chell and Frisén, 2012; Moss and Toni, 2013). In that context, it's well-accepted that brain trauma alters neurogenesis (Perry et al., 2015; Stein et al., 2015). In the past decade, the relationship between GABA neurotransmission and neurogenesis has been well-established. Ge and collaborators have shown that GABA receptors are expressed in the progenitor cells and that GABA itself, either ambient or synaptically-released GABA, could act at different steps during neurogenesis from proliferation to cell differentiation and finally synaptic integration (Ge et al., 2006; Anacker and Hen, 2017). In addition, the GABAergic polarity acts on the cell integration (Ge et al., 2006) but also in cell proliferation (Sun et al., 2012), thus establishing a causal link between cell cycling and cell cycle exit on depolarizing GABA condition (Scharfman and Bernstein, 2015; Hu J.J. et al., 2017). Apart from the monoamine hypothesis, a new theory based on the GABA release itself has been proposed to contribute to depression. GABA release has been demonstrated to be impaired in psychiatric disorders and particularly in depression (Luscher et al., 2011; Gabbay et al., 2012). More particularly, the GABAergic receptors have been shown to be decreased in expression and function in the dentate gyrus of depressed patients (Luscher et al., 2011; Lüscher and Fuchs, 2015) and brain tissues collected from suicide patients with a history of depression and anxiety (Merali et al., 2004). One of the first phenomenon linking depression and the hippocampus is the change in hippocampal volume observed both in rodent and in human (Savitz et al., 2010; Schuhmacher et al., 2013; Roddy et al., 2018). This is a common trait observed when the hypothalamic-pituitary-adrenal (HPA) axis is impaired. Other brain regions such as cingulate cortex, prefrontal cortex or even amygdala are also associated with depression (Drevets et al., 2008). In addition to volume changes other functions are changed in the hippocampus of animal displaying DLB, e.g., modified volume (Roddy et al., 2018), impaired GABAergic function (Merali et al., 2004), increase in excitability and monoamine dysfunction (Samuels et al., 2015) as well as impaired secondary neurogenesis and cognitive deficit (Ferguson et al., 2016; Anacker and Hen, 2017). Taken together, this makes the hippocampal formation a important and valuable structure to study depression in TBI models.
Parvalbumin-containing interneurons are the principal source of GABA release within the dentate gyrus and thus potential candidates to explain controlled-cortical impact (CCI)-induced dysregulations through their role in the synchronicity of hippocampal networks (Curia et al., 2008; Drexel et al., 2011; Shiri et al., 2014). Moreover, it is accepted that the activity of this class of interneurons could act on secondary neurogenesis by providing a source of ambient GABA (Song et al., 2012; Butler et al., 2016; Hu D. et al., 2017; Pérez-Domínguez et al., 2017), but little is known about the relationship that exists between parvalbumin-containing interneurons and the establishment of post-traumatic depression (Earnheart et al., 2007; Luscher et al., 2011; Fenton, 2015). Moreover, in human depression, their action is far from being established (Khundakar et al., 2011; Pehrson and Sanchez, 2015; Smiley et al., 2016).
Interestingly, the NKCC1 chloride importer antagonist bumetanide has been shown to attenuate many disorders like ASD, Parkinson's disease, and schizophrenia as well as some CCI-induced consequences. This stresses the therapeutic potential of restoring low (Cl-)i levels and an efficient GABAergic inhibition (Lemonnier et al., 2013, 2016; Damier et al., 2016; Xu et al., 2016; Ben-Ari, 2017). Although, it has been previously shown that bumetanide could have various positive effects on TBI models (Hui et al., 2016; Zhang et al., 2017) and could also act on secondary neurogenesis in stroke condition (Xu et al., 2016), yet nothing is known about the early action of this compound prior to the establishment of depressive-like behaviors (DLB). Our results showed that brain trauma disrupts chloride homeostasis, leading to hippocampal network disturbances and impaired neurogenesis associated with DLB. Early restoration of chloride homeostasis, using the NKCC1 inhibitor bumetanide rapidly after trauma, attenuates the severity of post-traumatic alterations notably by reducing interneuron loss. This, taken together, suggests a therapeutic potential of this FDA-approved compound after trauma.