Combined effect of trifluoperazine and sodium cromoglycate on reducing acute edema and limiting lasting functional impairments after spinal cord injury in rats.

Edema formation is one of the very first events to occur after spinal cord injury (SCI) leading to an increase of the intrathecal pressure and consequently to serious spinal tissue and functional impairments. Current edema treatments are still symptomatic and/or non-specific. Since edema formation mechanisms are mainly described as vasogenic and cytotoxic, it becomes crucial to understand the interplay between these two subtypes. Acting on key targets to inhibit edema formation may reduce secondary damage and related functional impairments. In this study, we characterize the edema kinetic after T9-10 spinal contusion. We use trifluoperazine (TFP) to block the expression and the functional subcellular localization of aquaporin-4 supposed to be implicated in the cytotoxic edema formation. We also use sodium cromoglycate (SCG) to deactivate mast cell degranulation known to be implicated in the vasogenic edema formation. Our results show a significant reduction of edema after TFP treatment and after TFP-SCG combined treatment compared to control. This reduction is correlated with limited onset of initial sensorimotor impairments particularly after combined treatment. Our results highlight the importance of potential synergetic targets in early edema therapy after SCI as part of tissue sparing strategies.

Targeting Mast Cells: Sodium Cromoglycate as a Possible Treatment of Lipedema.

Background: Mast cells are immune cells that mediate hypersensi-tivity and allergic reactions in the body, secreting histamine and other inflammatory molecules. They have been associated with different inflammatory conditions such as obesity and other adipose tissue di-sorders. Lipedema is a chronic disease characterized by an abnormal accumulation of adipose tissue on the legs and arms, pain, and other symptoms. Mast cells may play a role in the pathology of lipedema. Objective: Pilot study to determine levels of histamine and its metabolites in lipedema subcutaneous adipose tissue (SAT) biopsy samples, and to test sodium cromoglycate for the treatment of mast cells in women with lipedema. Methods: Biopsies from lipedema and control SAT were collected and analyzed histologically for the presence of mast cells. Mass spec-trometry was used to measure the levels of histamine, a key marker of mast cells, and its metabolites in SAT in women with lipedema and controls, and after a group of women with lipedema were administered oral and topical doses of sodium cromoglycate for two weeks. Results: Histological examination of biopsies from lipedema patients confirmed the presence of mast cells. Metabolomic analysis revealed high levels of histamine and its metabolites in samples from women with lipedema compared to controls. Following a two-week treatment period, lipedema tissue samples exhibited reduced levels of histamine, suggesting a reduction of mast cell activity. Conclusion: Sodium cromoglycate has the ability to stabilize mast cells and reduce histamine levels in lipedema patients, which could be useful in lowering the symptoms of lipedema.

Stabilizing histamine release in gut mast cells mitigates peripheral and central inflammation after stroke.

Stroke is the most common cause of long-term disability and places a high economic burden on the global healthcare system. Functional outcomes from stroke are largely determined by the extent of ischemic injury, however, there is growing recognition that systemic inflammatory responses also contribute to outcomes. Mast cells (MCs) rapidly respond to injury and release histamine (HA), a pro-inflammatory neurotransmitter that enhances inflammation. The gut serves as a major reservoir of HA. We hypothesized that cromolyn, a mast cell stabilizer that prevents the release of inflammatory mediators, would decrease peripheral and central inflammation, reduce MC trafficking to the brain, and improve stroke outcomes. We used the transient middle cerebral artery occlusion (MCAO) model of ischemic stroke in aged (18 mo) male mice to investigate the role of MC in neuroinflammation post-stroke. After MCAO we treated mice with 25 mg/kg body weight of cromolyn (MC stabilizer) by oral gavage. Cromolyn was administered at 3 h, 10 h, 24 h and every 24 h for 3 days post-stroke. Three control groups were used. One group underwent a sham surgery and was treated with cromolyn, one received sham surgery with PBS vehicle and the third underwent MCAO with PBS vehicle. Mice were euthanized at 24 h and 3 days post-stroke. Cromolyn administration significantly reduced MC numbers in the brain at both 24 h and 3 days post-stroke. Infarct volume was not significantly different between groups, however improved functional outcomes were seen at 3 days post-stroke in mice that received cromolyn. Treatment with cromolyn reduced plasma histamine and IL-6 levels in both the 24-h and 3-day cohorts. Gut MCs numbers were significantly reduced after cromolyn treatment at 24 h and 3 days after stroke. To determine if MC trafficking from the gut to the brain occurred after injury, GFP+MCs were adoptively transferred to c-kit-/- MC knock-out animals prior to MCAO. 24 h after stroke, elevated MC recruitment was seen in the ischemic brain. Preventing MC histamine release by cromolyn improved gut barrier integrity and an improvement in stroke-induced dysbiosis was seen with treatment. Our results show that preventing MC histamine release possesses prevents post-stroke neuroinflammation and improves neurological and functional outcomes.

The Interactions of Magnesium Sulfate and Cromoglycate in a Rat Model of Orofacial Pain; The Role of Magnesium on Mast Cell Degranulation in Neuroinflammation.

Mast cell degranulation impacts the development of pain and inflammation during tissue injury. We investigated the antinociceptive effect of a combination of cromoglycate and magnesium in the orofacial model of pain and the histological profile of the effect of magnesium in orofacial pain. In male Wistar rats, formalin (1.5%, 100 µL) was injected subcutaneously into the right upper lip of rats after cromoglycate and/or magnesium. Pain was measured as the total time spent on pain-related behavior. Toluidine blue staining was used to visualize mast cells under the light microscope. In the formalin test, in phase 1, magnesium antagonized the antinociceptive effect of cromoglycate, while in phase 2, it potentiated or inhibited its effect. Magnesium significantly reduced mast cell degranulation in the acute phase by about 23% and in the second phase by about 40%. Pearson's coefficient did not show a significant correlation between mast cell degranulation and pain under treatment with magnesium. The cromoglycate-magnesium sulfate combination may prevent the development of inflammatory orofacial pain. The effect of a combination of cromoglycate-magnesium sulfate depends on the nature of the pain and the individual effects of the drugs. Magnesium reduced orofacial inflammation in the periphery, and this effect did not significantly contribute to its analgesic effect.

Case Report of Anal Fissures and Hemorrhoids Treated with Compounded Cromolyn Sodium and Naltrexone Hydrochloride in MEDISCA's SPG SUPPOSI-BASE.

The purpose of this case report is to evaluate and demonstrate the benefits of compounded therapy in treating chronic rectal fissures with hemorrhoids using a compounded suppository containing cromolyn sodium and naltrexone hydrochloride in MEDISCA's SPG SUPPOSI-BASE. The primary outcomes of symptomatic improvement and healed fissure were reported and confirmed by the practitioner and, via self-assessment, by the patient, which was observed after a long-troubled history of failed treatments. The case had no side effects or complications, and the patient reported a full recovery after using this compounded therapy for ten days.

The Investigation of Therapeutic Implications of Mast Cell Stabilizer Cromolyn Sodium on Cholestasis and Cholestatic Pruritus in Experimental Cholestasis.

BACKGROUND: Relevant studies have indicated that hepatic mast cells may have potential roles in the progression of cholestasis and cholestasis-induced itch. We aimed to compare the effects of cromolyn sodium and other medications on cholestatic pruritus, serum biochemistry, histamine, total bile acids, autotaxin, liver histopathology, and mast cell distribution in tissues in an experimental cholestasis model conducted by bile duct ligation. METHODS: Rats received the determined treatment consecutively for 10 days in addition to bile duct ligation. On the 5th and 10th days of the experiment, the rats' itching behaviors were observed for 5 minutes. After 10 days, blood and tissue samples were taken. RESULTS: Significant decreases in serum histamine and autotaxin levels, plasma total bile acids, total bilirubin, and biliary enzymes were reported only in cromolyn sodium-treated rats compared to the control group. In immunohistochemistry of the liver samples, the peribiliary mast cells stained positive for autotaxin. Except for bile duct infarctus, all histopathological findings of cholestasis significantly improved only in cromolyn sodium-treated and sertraline-treated rats. The liver and peritoneal mast cells significantly decreased only in cromolyn sodium-treated rats compared to the control group. On the 10th day of the experiment, the mean duration of itching was significantly lower in all groups, except for naloxone- and ondansetron-treated rats. CONCLUSION: Cromolyn sodium has promising antipruritic efficacy and provides biochemical and histopathological recovery of the relevant parameters of cholestasis induced by bile duct ligation. For the first time in the literature, we showed that peribiliary mast cells can produce autotaxin, which is a very important pruritogenic signal in the setting of cholestasis.

Cromolyn chitosan nanoparticles reverse the DNA methylation of RASSF1A and p16 genes and mitigate DNMT1 and METTL3 expression in breast cancer cell line and tumor xenograft model in mice.

BACKGROUND: Developing epigenetic drugs for breast cancer (BC) remains a novel therapeutic approach. Cromolyn is a mast cell stabilizer emerging as an anticancer drug; its encapsulation in chitosan nanoparticles (CSNPs) improves its effect and bioavailability. However, its effect on DNA and RNA methylation machineries has not been previously tackled. METHODS: The possible anticancer effect of cromolyn CSNPs and its potential as an epigenetic drug was investigated in vitro using MCF-7 human BC cell line and in vivo using Ehrlich ascites carcinoma-xenograft model in mice symbolizing murine mammary adenocarcinoma. Mice were injected with a single dose of Ehrlich ascites carcinoma cells subcutaneously for the induction of tumor mass, and then randomized into three groups: control, cromolyn CSNPs (equivalent to 5 mg cromolyn/kg, i.p.) and plain CSNPs twice/week for 2 weeks. RESULTS: Cromolyn CSNPs showed prominent anticancer effect in MCF-7 cells by reducing the cell viability percent and enhancing DNA damage in the comet assay demonstrating its apoptotic actions. Mechanistically, cromolyn CSNPs influenced potential epigenetic processes through mitigating DNA methyltransferase 1 (DNMT1) expression, reversing the hypermethylation pattern of the tumor suppressor RASSF1A and p16 genes and attenuating the expression of the RNA N6-methyladenosine writer, methyltransferase-like 3 (METTL3). Cromolyn CSNPs diminished ERK1/2 phosphorylation, a possible arm influencing DNMT1 expression. In vivo, cromolyn CSNPs lessened the tumor volume and halted DNMT1 and METTL3 expression in Ehrlich carcinoma mice. CONCLUSIONS: Cromolyn CSNPs have the premise as an epigenetic drug through inhibiting ERK1/2 phosphorylation/DNMT1/DNA methylation and possibly impacting the RNA methylation machinery via mitigating METTL3 expression.

Comparison of Cromolyn Sodium, Montelukast, and Zafirlukast Prophylaxis for Capsular Contracture.

BACKGROUND: Capsular contracture is the most common complication following breast augmentation. Recently, prophylaxis studies aiming to inhibit the release of profibrotic substances to prevent capsular contracture have gained in importance. This study investigated the effects of cromolyn sodium, montelukast, and zafirlukast on capsular contracture in a rat model. METHODS: Thirty female Wistar albino rats were randomly divided into five groups: control, sham, cromolyn sodium, montelukast, and zafirlukast. Intraperitoneal injections were administered daily to the sham (1 ml per day), cromolyn sodium (10 mg/kg per day), montelukast (10 mg/kg per day), and zafirlukast (1.25 mg/kg per day) groups 1 month before surgery. Miniature breast implants were then placed on the backs of the rats in each group. Injections were continued for the next 3 months. The rats were subsequently killed, and the capsules were harvested and assessed histopathologically. The histopathologic outcomes were acute inflammation status, inflammation severity, synovial metaplasia, foreign body reaction, mast cell count, and capsular thickness. RESULTS: The cromolyn sodium, montelukast, and zafirlukast groups had less acute inflammation and lower mean inflammation severity scores, foreign body reaction occurrence, mast cell counts, and capsular thickness than the control and sham groups ( p < 0.05). These parameters were better in the cromolyn sodium group than in the montelukast and zafirlukast groups ( p < 0.05). CONCLUSIONS: Cromolyn sodium appears to inhibit capsular contracture more efficiently than montelukast and zafirlukast. This report may be a pioneer study for the prophylactic use of cromolyn sodium in capsular contracture. CLINICAL RELEVANCE STATEMENT: The prophylactic administration of cromolyn sodium appears to reduce capsular contracture more efficiently than that of montelukast and zafirlukast. This report might constitute a pioneer study for the prophylactic use of cromolyn sodium in capsular contracture.

Cromolyn Sodium differentially regulates human mast cell and mouse leukocyte responses to control allergic inflammation.

BACKGROUND: Cromolyn Sodium (CS) has been used in the past as an anti-allergy drug owing to its mast cell (MC) stabilizing properties that impair histamine release. However, additional mechanisms for its clinical actions are likely and might help to identify new roles for MCs and leukocytes in regulating inflammation. Here, using human cord blood-derived MCs (CBMCs), mouse bone marrow-derived MCs (BMMCs) and eosinophils (BMEos), and in vivo mouse models of allergic inflammation (AI), additional actions of CS on MCs were determined. METHODS: The in vitro effects of CS on IgE-activated human and mouse MCs were assessed by measuring the levels of pro-inflammatory (tryptase, LTC4, IL-8, CD48) and pro-resolution effectors (IL-10, CD300a, Annexin A1) before and after CS treatment. The in vivo effects of daily CS injections on parameters of inflammation were assessed using mouse models of allergic peritonitis (AP) (Ovalbumin/Alum- or Ovalbumin/S. aureus enterotoxin B) and allergic airways inflammation (AAI) (house dust mite (HDM)). RESULTS: In vitro, CS did not affect pro-inflammatory effectors but significantly increased the anti-inflammatory/pro-resolution CD300a levels and IL-10 release from IgE-activated CBMCs. BMMCs were not affected by CS. In vivo, CS injections decreased total cell and Eos numbers in the peritoneal cavity in the AP models and bronchoalveolar lavage and lungs in the AAI model. CS reduced EPX release from PAF-activated BMEos in vitro, possibly explaining the in vivo findings. CONCLUSION: Together, these results demonstrate immunomodulatory actions for CS in AI that are broader than only MC stabilization.

Effects of Disodium Cromoglycate Treatment in the Early Stage of Diabetic Nephropathy: Focus on Collagen Deposition.

Inflammation is part of the pathophysiology of diabetic nephropathy (DN), and mast cells (MCs) appear to increase in number within the kidney of humans and animals with diabetes. Disodium cromoglycate (CG) not only inhibits the degranulation of MCs but also has several secondary effects that may improve inflammation. However, little is known about the effects of CG treatment on kidney collagen deposition and myofibroblast population in animals with type I diabetes (DM1). Data presented here suggest that the increases in the density and activity of MCs within the kidney in the early stages of DN contribute to tubulointerstitial collagen deposition, even in the absence of alterations in the renal myofibroblast population. Moreover, CG treatment showed renoprotective effects in rats with DM1, which appear to be linked to its mast cell stabilizing property and its ability to avoid some detrimental morphofunctional alterations.

Mast cell function in prostate inflammation, fibrosis, and smooth muscle cell dysfunction.

Intraurethral inoculation of mice with uropathogenic Escherichia coli (CP1) results in prostate inflammation, fibrosis, and urinary dysfunction, recapitulating some but not all of the pathognomonic clinical features associated with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). In both patients with LUTS and CP1-infected mice, we observed increased numbers and activation of mast cells and elevated levels of prostate fibrosis. Therapeutic inhibition of mast cells using a combination of a mast cell stabilizer, cromolyn sodium, and the histamine 1 receptor antagonist cetirizine di-hydrochloride in the mouse model resulted in reduced mast cell activation in the prostate and significant alleviation of urinary dysfunction. Treated mice showed reduced prostate fibrosis, less infiltration of immune cells, and decreased inflammation. In addition, as opposed to symptomatic CP1-infected mice, treated mice showed reduced myosin light chain-2 phosphorylation, a marker of prostate smooth muscle contraction. These results show that mast cells play a critical role in the pathophysiology of urinary dysfunction and may be an important therapeutic target for men with BPH/LUTS.NEW & NOTEWORTHY LUTS-associated benign prostatic hyperplasia is derived from a combination of immune activation, extracellular matrix remodeling, hyperplasia, and smooth muscle cell contraction in prostates of men. Using a mouse model, we describe the importance of mast cells in regulating these multiple facets involved in the pathophysiology of LUTS. Mast cell inhibition alleviates both pathology and urinary dysfunction in this model, suggesting the potential for mast cell inhibition as a therapeutic that prevents and reverses pathology and associated symptomology.

From Combinations to Single-Molecule Polypharmacology-Cromolyn-Ibuprofen Conjugates for Alzheimer's Disease.

Despite Alzheimer's disease (AD) incidence being projected to increase worldwide, the drugs currently on the market can only mitigate symptoms. Considering the failures of the classical paradigm "one target-one drug-one disease" in delivering effective medications for AD, polypharmacology appears to be a most viable therapeutic strategy. Polypharmacology can involve combinations of multiple drugs and/or single chemical entities modulating multiple targets. Taking inspiration from an ongoing clinical trial, this work aims to convert a promising cromolyn-ibuprofen drug combination into single-molecule "codrugs." Such codrugs should be able to similarly modulate neuroinflammatory and amyloid pathways, while showing peculiar pros and cons. By exploiting a linking strategy, we designed and synthesized a small set of cromolyn-ibuprofen conjugates (4-6). Preliminary plasma stability and neurotoxicity assays allowed us to select diamide 5 and ethanolamide 6 as promising compounds for further studies. We investigated their immunomodulatory profile in immortalized microglia cells, in vitro anti-aggregating activity towards Aß42-amyloid self-aggregation, and their cellular neuroprotective effect against Aß42-induced neurotoxicity. The fact that 6 effectively reduced Aß-induced neuronal death, prompted its investigation into an in vivo model. Notably, 6 was demonstrated to significantly increase the longevity of Aß42-expressing Drosophila and to improve fly locomotor performance.

Eosinophilic colitis: an infrequent disease with difficult diagnose.

Eosinophilic colitis (EC) is a rare entity. It is part of eosinophilic gastroenteritis, a rare inflammatory disorder characterised by eosinophilic infiltration of tissues that can affect any segment of the digestive tract. The diagnosis is established by the presence of an increased eosinophilic infiltrate in the colon wall in symptomatic patients. There is no characteristic clinical picture of EC. It can be associated with abdominal pain, changes in bowel movements, diarrhoea and rectal bleeding. Biopsies are mandatory if EC is suspected and despite visualising a normal mucosa. Although there are no protocol guidelines in this regard, steroid treatment is the first option in controlling the disease. Increasing the knowledge of clinicians and pathologists of this disorder and the recording its real incidence and population impact, could improve the understanding and treatment of the disease.

Effect of Sodium Cromoglycate on Acetic Acid-induced Ulcerative Colitis in Mice.

Background/Aims: Ulcerative colitis (UC) is a type of inflammatory bowel disease that mainly involves the colon. Thus far, glucocorticoids and amino-salicylate have been the main treatment. Methods: To assess drugs with fewer side effects, this study evaluated the effects of sodium cromoglycate (SCG) on acetic acid-induced UC in rats. The treatment groups included SCG receivers (50 and 100 mg/kg, intra-orally) and sulfasalazine (SSZ) receivers (100 mg/kg, intra-orally). The colonic mucosal injury was assessed by clinical, macroscopic, and histopathological examinations. Results: In the treatment groups with 50 and 100 mg/kg of SCG, the clinical activity score decreased to 2.67±0.18 and 1.73±0.21 (p<0.05), respectively, compared to the UC control group (3.21±0.31), and were higher than that of the group given the standard treatment of 100 mg/kg SSZ (1.10±0.09). The treatment groups with 50 and 100 mg/kg of SCG showed a lower clinical gross lesion score than the UC control group (2.91±0.28 and 2.10±0.43, vs. 4.49±0.61, p<0.05) and were higher than the standard group (0.95±0.18). Treatment with SCG (100 mg/kg) decreased the macroscopic scores significantly compared to the UC control group (p<0.05) on the 8th day. Conclusions: SCG (100mg/kg) decreased significantly the clinical activity score, gross lesion, and percentage-affected area compared to the UC controls on the 8th day.

Cromolyn sodium delays disease onset and is neuroprotective in the SOD1G93A Mouse Model of amyotrophic lateral sclerosis.

Accumulating evidence suggests that neuroinflammatory processes are implicated in the initiation and progression of amyotrophic lateral sclerosis (ALS). Previous reports have demonstrated an increase in microgliosis and astrogliosis in the lumbar spinal cord of SOD1G93A transgenic mice before the onset of symptoms, a neuroinflammatory response which correlated with disease progression. Importantly, early stage homeostatic microglia enhanced motor neuron survival, while pro-inflammatory microglia were toxic to motor neurons in the SOD1G93A mice. Recent studies from our group have demonstrated that cromolyn sodium, an FDA approved compound, exerts neuroprotective effects in mouse models of Alzheimer's disease by altering microglial cell activation. Here, we tested the neuroprotective and anti-inflammatory effects of cromolyn sodium in the SOD1G93A mouse model of ALS. Our results indicate that cromolyn sodium treatment significantly delayed the onset of neurological symptoms, and improved deficits in PaGE performance in both male and female mice, however, there was only an effect on survival in female mice. Furthermore, there was a significant increase in motor neuron survival in the lumbar spinal cord as well as a significant decrease in the denervation of the neuromuscular junction of the tibialis anterior muscle in cromolyn treated transgenic SOD1G93A mice. Lastly, cromolyn treatment decreased the expression of pro-inflammatory cytokines/chemokines in the lumbar spinal cord and plasma and decreased mast cell degranulation in the tibialis anterior muscle of transgenic SOD1G93A mice. Together, these findings suggest that cromolyn sodium provides neuroprotection in the SOD1G93A mice by decreasing the inflammatory response.

Exercise-Induced bronchoconstriction and therapeutic modulation in Iraqi Girls Intermediate School Students

EIB (Exercise-Induced Bronchoconstriction) describes the narrowing that accurs in the airway follow a short period of exercise. EIB is found in 8-10% of normal children population as occult bronchospasm during or after physical activities. The mecanisms of EIB are related to rapid ventilation and mouth brathing which cause beat and water loss during breathing leading to bronchoconstriction. Peak Expiratory Flow Rate (PEFR) measured pre and post-exercise in students aged 12-16 years in girl intrmediate school. Any female shows PEFR values reduction 15% after 6 minutes continuous free running considered as asthmatic patient, this give an incidence rate of asthmatic patient of 9% in female students in this age. Treatment of EIB, Zafirlukast treatment gives (85.7%) protection rate. While salbutamol inhalation gives a protection rate 88%. Only 66.6% of girls with EIB give an improvement in PEFR values after sodium cromoglycate treatment. A regular measurement of PEFR in school students appears to be a good indicator of EIB, while inhalation of salbutaol 15 minutes before exercise give a good protection against EIB attacks at least for 4 hours (AU)

Mast Cell Activation Syndrome and Mastocytosis: Initial Treatment Options and Long-Term Management.

Patients with clonal mast cell activation syndromes (MCAS) including cutaneous and systemic mastocytosis (SM) may present with symptoms of mast cell activation, but in addition can have organ damage from the local effects of tissue infiltration by clonal mast cells. Patients with nonclonal MCAS may have chronic or episodic mast cell activation symptoms with an increase in serum tryptase and/or urinary metabolites of histamine, prostaglandin D2, and leukotrienes. Symptoms of MCAS and SM can be managed by blockade of mediator receptors (H1 and H2 antihistamines, leukotriene receptor blockade), inhibition of mediator synthesis (aspirin, zileuton), mediator release (sodium cromolyn), anti-IgE therapy, or a combination of these approaches. Acute episodes of mast cell activation require epinephrine, and prolonged episodes may be addressed with corticosteroids. Patients with clonal mast cell syndromes may need a reduction in the number of mast cells to prevent severe symptoms including anaphylaxis and/or progression to aggressive diseases.

Sodium cromoglycate reduces short- and long-term consequences of status epilepticus in rats.

Several studies indicate that sodium cromoglycate (CG) induces neuroprotective effects in acute neurological conditions. The present study focused on investigating if the use of CG in rats during the post-status epilepticus (post-SE) period reduces the acute and long-term consequences of seizure activity. Our results revealed that animals that received a single dose of CG (50 mg/kg s.c.: subcutaneously) during the post-SE period showed a lower number of neurons in the process of dying in the dentate gyrus, hilus, cornu ammonis 1 (CA1), and CA3 of the dorsal hippocampus than the rats that received the vehicle. However, this effect was not evident in layers V-VI of the sensorimotor cortex or the lateral-posterior thalamic nucleus. A second experiment showed that animals that received CG subchronically (50 mg/kg s.c. every 12 h for 5 days followed by 24 mg/kg/day s.c. for 14 days using osmotic minipumps) after SE presented fewer generalized convulsive seizures and less neuronal damage in the lateral-posterior thalamic nucleus but not in the hippocampus or cortex. Our data indicate that CG can be used as a therapeutic strategy to reduce short- and long-term neuronal damage in the hippocampus and thalamus, respectively. The data also indicate that CG can reduce the expression of generalized convulsive spontaneous seizures when it is given during the latent period of epileptogenesis.