Beta-caryophyllene mitigates the cognitive impairment caused by repeated exposure to aspartame in rats: Putative role of BDNF-TrKB signaling pathway and acetylcholinesterase activity.

Aspartame (ASP) is a common sweetener, but studies show it can harm the nervous system, causing learning and memory deficits. ß-caryophyllene (BCP), a natural compound found in foods, including bread, coffee, alcoholic beverages, and spices, has already described as a neuroprotector agent. Remarkably, ASP and BCP are commonly consumed, including in the same meal. Therefore, considering that (a) the BCP displays plenty of beneficial effects; (b) the ASP toxicity; and (c) that they can be consumed in the same meal, this study sought to investigate if the BCP would mitigate the memory impairment induced by ASP in rats and investigate the involvement of the brain-derived neurotrophic factor (BDNF)/ tropomyosin receptor kinase B (TrKB) signaling pathway and acetylcholinesterase (AChE) activity. Young male Wistar rats received ASP (75 mg/kg; i.g.) and/or BCP (100 mg/kg; i.p.) once daily, for 14 days. At the end of the treatment, the animals were evaluated in the open field and object recognition tests. The cerebral cortex and hippocampus samples were collected for biochemical and molecular analyses. Results showed that the BCP effectively protected against the cognitive damage caused by ASP in short and long-term memories. In addition, BCP mitigated the increase in AChE activity caused by ASP. Molecular insights revealed augmented BDNF and TrKB levels in the hippocampus of rats treated with BCP, indicating greater activation of this pathway. In conclusion, BCP protected against ASP-induced memory impairment. AChE activity and the BDNF/TrkB signaling pathway seem to be potential targets of BCP modulatory role in this study.

A 24-year-Old Male with Marden-Walker Syndrome and Epilepsy: Case Report.

We report a 24-year-old male with blepharophimosis, psychomotor retardation, brachycephaly, microstomia, immobile face, high arched palate, single palmar crease, kyphoscoliosis, talipes equinovarus, inguinal hernia, pyloric stenosis, recurrent infections, bilateral camptodactyly, wide-set eyes, decreased muscle mass, hypotonia, exotropia, and ptosis in the left eye, growth retardation, multiple congenital contractures, and hyporreflexia. Contractures improved with aging, but intellectual disability and blepharophimosis remained. He also presented epilepsy, outbursts of laughter, and predisposition to drug adverse effects (skin lesions with carbamazepine and secondary parkinsonism).

Intermittent Exposure to Aflatoxin B1 Did Not Affect Neurobehavioral Parameters and Biochemical Markers of Oxidative Stress.

Aflatoxin B1 (AFB1) is the most common toxic mycotoxin that contaminates food. The treatment of its intoxication and the management of contaminations are a constant subject of health agendas worldwide. However, such efforts are not always enough to avoid population intoxication. Our objective was to investigate whether intermittent exposure to AFB1 would cause any impairment in biochemical and behavioral parameters, intending to simulate an irregular consumption. Male Wistar rats received four AFB1 administrations (250 µg/kg) by intragastric route separated by a 96-h interval. Toxicity was evaluated using behavioral tests (open field, object recognition, nest construction, marble burying, and splash test), biochemical markers of oxidative stress (cerebral cortex, hippocampus, liver, and kidneys), and plasma parameters of hepatic and renal functions. The intermittent exposure caused no modification in body weight gain as well as in organ weight. Both control and AFB1 groups presented similar profiles of behavior to all tests performed. Furthermore, AFB1 administrations alter neither antioxidant defenses nor markers of oxidation in all assayed tissues and in the plasma markers of hepatic and renal functions. Therefore, AFB1 intermittent administration did not cause its common damage from exposure to this toxicant, which must be avoided, and additional studies are required.

Repeated co-exposure to aflatoxin B1 and aspartame disrupts the central nervous system homeostasis: Behavioral, biochemical, and molecular insights.

Several studies demonstrated the toxicity of aspartame (ASP) and aflatoxin B1 (AFB1 ) in preclinical models. Although the majority of these reports assessed the toxic effects of each substance separately, their concomitant exposure and hazardous consequences are scarce. Importantly, the deleterious effects at the central nervous system caused by ASP and AFB1 co-exposure are rarely addressed. We evaluated if concomitant exposure to AFB1 and ASP would cause behavioral impairment and alteration in oxidative status of the brain in male rats. Animals received once a day for 14 days AFB1 (250 µg/kg, intragastric gavage [i.g.]), ASP (75 mg/kg, i.g.), or both substances (association). On day 14, they were subjected to behavioral evaluation, and biochemical and molecular parameters of oxidative status were measured in the cerebral cortex and hippocampus. In the open field test, AFB1 and combination treatments modified the motor, exploratory, and grooming behavior. In the splash test, all treatments caused a reduction in grooming time compared to the control group. An increase in thiobarbituric acid-reactive substances content induced by AFB1 and combination treatments was observed. The antioxidant defenses (vitamin C, nonprotein sulfhydryl, and ferric reducing antioxidant power) were impaired in all groups compared to control. Regarding molecular evaluation, mitochondrial superoxide dismutase-2 immunoreactivity decreased after AFB1 or ASP exposition in the hippocampus. Thus, co-exposure to ASP and AFB1 was potentially more toxic because it aggravated behavioral impairments and oxidative status disbalance in comparison to the groups that received only ASP or AFB1 . Therefore, our data suggest that those substances caused a disruption in brain homeostasis.

Beneficial Effects of Rosmarinic Acid In Vitro and In Vivo Models of Epileptiform Activity Induced by Pilocarpine.

Epilepsy is characterized by a predisposition to generate recurrent and spontaneous seizures; it affects millions of people worldwide. Status epilepticus (SE) is a severe type of seizure. In this context, screening potential treatments is very important. In the present study, we evaluated the beneficial effects of rosmarinic acid (RA) in pilocarpine-induced in vitro and in vivo models of epileptiform activity. Using an in vitro model in combined entorhinal cortex-hippocampal from Wistar rats we evaluated the effects of RA (10 µg/mL) on the lactate release and a glucose fluorescent analogue, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NDBG), after incubation in high potassium aCSF supplemented or not with pilocarpine. In the in vivo model, SE was induced in male C57BL/6 mice by pilocarpine. At 1, 24, and 48 h after the end of SE mice were treated with RA (30 mg/kg/v.o.). We evaluated the neuromotor impairment by neuroscore tests and protein carbonyl levels in the cerebral cortex. In both in vitro models, RA was able to decrease the stimulated lactate release, while no effect on 2-NBDG uptake was found. RA has beneficial effects in models of epileptiform activity in vivo and in vitro. We found that RA treatment attenuated SE-induced neuromotor impairment at the 48 h timepoint. Moreover, post-SE treatment with RA decreased levels of protein carbonyls in the cerebral cortex of mice when compared to their vehicle-treated counterparts. Importantly, RA was effective in a model of SE which is relevant for the human condition. The present data add to the literature on the biological effects of RA, which could be a good candidate for add-on therapy in epilepsy.

Worst spasticity in patients post-stroke associated with MNSOD ALA16VAL polymorphism and interleukin-1ß.

The MnSOD Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to risk factors of several metabolic and vascular diseases. However, little is known about interaction between MnSOD Ala16Val SNP in stroke, a frequent neurologic disease that involves clinic manifestations such as motor deficits and spasticity. In this sense, we decided to investigate the relationship between MnSOD Ala16Val SNP with spasticity in stroke and also its influence on interleukin levels, BDNF, and glycolipid parameters. Eighty post-stroke subjects and 80 healthy controls were investigated. We showed a higher spasticity, levels of total cholesterol, LDL, IL-1ß, IL-6, and INF-γ in VV post-stroke group. Interesting, we found a correlation between IL-1ß levels and spasticity in VV post-stroke. Triglycerides, glucose levels and caspases (1 and 3) activation were significantly higher, as well as BDNF levels were lower in VV and AV post-stroke. DNA damage was higher in post-stroke group. Thus, we can suggest that the V allele has a worse glycolipid profile, which would facilitate changes in neurovascular homeostasis. These events associated with an increase in inflammatory markers and a reduction in BDNF can contribute with the stroke and a worse clinical evolution in relation to spasticity in patients with VV genotype.

Beta-caryophyllene attenuates short-term recurrent seizure activity and blood-brain-barrier breakdown after pilocarpine-induced status epilepticus in rats.

BACKGROUND: Status epilepticus (SE) is a neurological life-threatening condition, resulting from the failure of the mechanisms responsible for seizure termination. SE is often pharmacoresistant and associated with significant morbidity and mortality. Hence, ceasing or attenuating SE and its consequences is of fundamental importance. Beta-caryophyllene is a functional CB2 receptor agonist and exhibit a good safety profile. Besides, it displays beneficial effects in several experimental conditions, including neuroprotective activity. In the present study we aimed to investigate the effects of beta-caryophyllene on pilocarpine-induced SE. METHODS: Wistar rats were submitted to pilocarpine-induced SE and monitored for 24 h by video and EEG for short-term recurrence of seizure activity (i.e. seizures occurring within 24 h after termination of SE). Rats received beta-caryophyllene (100 mg/kg, ip) at 1, 8- and 16-hours after SE. Twenty-four hours after SE we evaluated sensorimotor response, neuronal damage (fluoro jade C staining) and serum albumin infiltration into brain parenchyma. RESULTS: Beta-caryophyllene-treated animals presented fewer short-term recurrent seizures than vehicle-treated counterparts, suggesting an anticonvulsant effect after SE. Behavioral recovery from SE and the number of fluoro jade C positive cells in the hippocampus and thalamus were not modified by beta-caryophyllene. Treatment with beta-caryophyllene attenuated the SE-induced increase of albumin immunoreactivity in the hippocampus, indicating a protective effect against blood-brain-barrier breakdown. CONCLUSIONS: Given the inherent difficulties in the treatment of SE and its consequences, present results suggest that beta-caryophyllene deserve further investigation as an adjuvant therapeutic strategy for SE.

Hepatic susceptibility to oxidative damage after repeated concomitant exposure to aspartame and aflatoxin B1 in rats.

The potential interactions among food additives/contaminants and the consequences to biological systems is a topic that is rarely addressed in scientific literature. Thus, the current study investigated if the combined administration of ASP and AFB1 would impair hepatic and renal oxidative status. Male Wistar rats received during 14 days once a day ASP (75 mg/Kg) and/or AFB1 (250 µg/Kg) through intragastric route. At the end of experimental protocol, samples of liver and kidneys were collected for assessing biochemical markers of oxidative status. In the hepatic tissue, the treatment with a single substance (ASP or AFB1) caused an increase in TBARS levels, and a reduction in non-enzymatic antioxidant defenses (Vit C and NPSH levels and FRAP test). In the kidneys, TBARS levels were increased only in the group that received ASP + AFB1. The association reduced NPSH content, while the treatment with AFB1 reduced the FRAP levels. GST and CAT activities were increased in all treatments. Overall, ASP and AFB1 association presented higher toxic effects to the tissues. To the best of our knowledge, this is the first study demonstrating that the associated use of both ASP and AFB1 induces more extensive injuries in comparison to the effects caused by each one alone. Therefore, these data demonstrated that concomitant exposure to ASP and AFB1 potentiated their oxidative damage in hepatic tissue, suggesting that this organ is particularly sensitive to the toxic action induced by these substances.

Physical Exercise as a Modulator of Vascular Pathology and Thrombin Generation to Improve Outcomes After Traumatic Brain Injury.

Disruption of the blood-brain barrier and occurrence of coagulopathy after traumatic brain injury (TBI) have important implications for multiple secondary injury processes. Given the extent of post-traumatic changes in neuronal function, significant alterations in some targets, such thrombin (a protease that plays a physiological role in maintaining blood coagulation), play an important role in TBI-induced pathophysiology. Despite the magnitude of thrombin in synaptic plasticity being concentration-dependent, the mechanisms underlying TBI have not been fully elucidated. The understanding of this post-injury neurovascular dysregulation is essential to establish scientific-based rehabilitative strategies. One of these strategies may be supporting physical exercise, considering its relevance in reducing damage after a TBI. However, there are caveats to consider when interpreting the effect of physical exercise on neurovascular dysregulation after TBI. To complete this picture, this review will describe how the interactions established between blood-borne factors (such as thrombin) and physical exercise alter the TBI pathophysiology.

Relationship between seizure type, metabolic profile, and inflammatory markers in blood samples of patients with epilepsy.

We investigated the metabolic profile, reactive species production, and inflammatory parameters in patients with epilepsy. Furthermore, we investigated whether there is any relationship between these parameters and seizure type. Patients with epilepsy (n=43) and healthy subjects (control group; n=41) were recruited to participate in the study. Initially, the participants were submitted to a clinical questionnaire and patients with epilepsy were classified according to seizure type. Metabolic markers and inflammatory and oxidative factors were also measured in specific blood samples. We compared these results with data from the control subjects. Statistical analyses showed that patients with epilepsy presented with higher levels of glycolipid, oxidative stress, and inflammatory parameters compared to the control subjects. Interestingly, patients with generalized seizures presented with higher MnSOD activity and metabolic parameters (total cholesterol, low-density lipoprotein, glucose and triglyceride levels) compared to the partial seizure and control groups. Furthermore, patients with generalized epilepsy demonstrated a significant correlation between TNF-α and caspase 8 (p<0.05), caspase 3 (p<0.05), and Picogreen (p<0.001). This study supports evidence that the levels of inflammatory, glycolipid, and oxidative factors are higher in epilepsy patients, especially those with generalized epilepsy.

Sustained glial reactivity induced by glutaric acid may be the trigger to learning delay in early and late phases of development: Involvement of p75NTR receptor and protection by N-acetylcysteine.

Degeneration of striatal neurons and cortical atrophy are pathological characteristics of glutaric acidemia type I (GA-I), a disease characterized by accumulation of glutaric acid (GA). The mechanisms that lead to neuronal loss and cognitive impairment are still unclear. The purpose of this study was to verify if acute exposure to GA during the neonatal period is sufficient to trigger apoptotic processes and lead to learning delay in early and late period. Besides, whether N-acetylcysteine (NAC) would protect against impairment induced by GA. Pups mice received a dose of GA (2.5 µmol/ g) or saline, 12 hs after birth, and were treated with NAC (250 mg/kg) or saline, up to 21th day of life. Although GA exhibited deficits in the procedural and working memories in 21 and 40-day-old mice, NAC protected against cognitive impairment. In striatum and cortex, NAC prevented glial cells activation (GFAP and Iba-1), decreased NGF, Bcl-2 and NeuN, the increase of lipid peroxidation and PARP induced by GA in both ages. NAC protected against increased p75NTR induced by GA, but not in cortex of 21-day-old mice. Thus, we showed that the integrity of striatal and cortical pathways has an important role for learning and suggested that sustained glial reactivity in neonatal period can be an initial trigger for delay of cognitive development. Furthermore, NAC protected against cognitive impairment induced by GA. This work shows that early identification of the alterations induced by GA is important to avoid future clinical complications and suggest that NAC could be an adjuvant treatment for this acidemia.

Characteristics of Post-Ictal Headaches in Patients with Epilepsy: a Longitudinal Study.

OBJECTIVES: This study aimed to investigate the clinical predictors of post-ictal headache (PIH) in patients with epilepsy in a tertiary center in Brazil. METHODS: 302 individuals with adult-onset epilepsy were followed for 9.8 years in our Hospital. Structured questionnaires about headaches were applied. The presence of PIH was the primary outcome. We used multilevel linear modeling in our data analysis. RESULTS: From the total, 46.3% had post-ictal headaches. Tension-type post-ictal headache was present in 55% (N = 77) of the subjects, migrainous in 32.1% (N = 45), and both types in 12.8% (N = 18). Family history of migraine (Odds ratio: 1.696; 95% CI: 1.372 to 2.096), diagnosis of drug-resistant epilepsy (Odds ratio: 1.169; 95% CI: 1.135 to 2.146), months since last visit (Odds ratio: 1.464; 95% CI: 1.243 to 2.888), and generalized seizure onset type of epilepsy (Odds ratio: 1.527; 95% CI: 1.114 to 1.668), were significant determinants of PIH on multilevel linear modeling. DISCUSSION: PIH are associated with drug-resistant epilepsy, generalized seizures, and family history of migraine. The rates of pos-ictal headaches could be influenced by the use of antiepileptic drugs.

MnSOD Ala16Val polymorphism in cognitive dysfunction in patients with epilepsy: A relationship with oxidative and inflammatory markers.

OBJECTIVE: The objective of the study was to evaluate the neurocognitive profile and its relation with Ala16ValMnSOD polymorphism in epilepsy and if these clinical parameters are linked to oxidative stress and inflammatory markers. METHODS: Patients with epilepsy (n = 31) and healthy subjects (n = 42) were recruited. A neuropsychological evaluation was performed in both groups through a battery of cognitive tests. Oxidative stress, inflammatory markers, apoptotic factors, and deoxyribonucleic acid (DNA) damage were measured in blood samples. RESULTS: Statistical analyses showed the association of MnSOD Ala16Val polymorphism with cognitive impairment, including praxis, perception, attention, language, executive functions, long-term semantic memory, short-term visual memory, and total memory in patients with epilepsy and Valine-Valine (VV) genotype compared with the control group. Compared with the controls and patients with epilepsy, Alanine-Alanine (AA), and Alanine-Valine (AV) genotype, the patients with epilepsy and VV genotype exhibited higher levels of tumor necrosis factor alpha (TNF-α), interleukin 1ß (IL-1ß), interleukin 6 (IL-6), activation of caspases 1 and 3 (CASP-1 and -3), and DNA damage. Our findings also showed higher carbonyl protein and thiobarbituric acid reactive substances (TBARS) levels as well as an increased superoxide dismutase (SOD) and acetylcholinesterase (AChE) activities in patients with epilepsy and VV genotype. CONCLUSION: This study supports the evidence of a distinct neuropsychological profile in patients with epilepsy, especially those with the VV genotype. Furthermore, our results suggest that oxidative and inflammatory pathways may be associated with genetic polymorphism and cognitive dysfunction in patients with epilepsy.

Capsaicin-sensitive fibers mediate periorbital allodynia and activation of inflammatory cells after traumatic brain injury in rats: Involvement of TRPV1 channels in post-traumatic headache.

Post-traumatic headache (PTH) is a condition that frequently affects individuals after traumatic brain injury (TBI). Inflammation is one of the major causes of this disability. However, little is known about the trigger for, and endurance of, this painful process. Thus, the involvement of fibers containing the transient receptor potential vanilloid 1 (TRPV1) channels on the PTH and inflammation after TBI through neonatal treatment with capsaicin are investigated. Fluid percussion injury (FPI) in adult male Wistar rats caused periorbital allodynia in one, three and seven days after injury, and the neonatal treatment reversed the painful sensation in seven days. The lack of TRPV1 channels reduced the activation of macrophages and glial cells induced by TBI in the trigeminal system, which were characterized by glial fibrillary acidic protein (GFAP) and ionized calcium binding adapter molecule-1 (IBA-1) immune content in the ipsilateral trigeminal ganglion, brainstem, and perilesional cortex. Immunofluorescence analyses of the ipsilateral Sp5C nucleus demonstrated a hypertrophic astrocytes profile after TBI which was reduced with treatment. Moreover, effects of succinate sumatriptan (SUMA - 1 mg/kg), TRPV1 selective antagonist capsazepine (CPZ - 2 mg/kg), and TRP non-selective antagonist ruthenium red (RR - 3 mg/kg) were evaluated. Although all mentioned drugs reduced the painful sensation, SUMA and CPZ demonstrated a stronger effect compared to the RR treatment, reinforcing the involvement of TRPV1 channels in periorbital allodynia after TBI. Hence, this report suggests that TRPV1-containing fibers and TRPV1 channels are able to induce inflammation of the trigeminal system and maintain the painful sensation after TBI.

The role of mitochondrial bioenergetics and oxidative stress in depressive behavior in recurrent concussion model in mice.

Traumatic brain injury (TBI) is a public health problem in which even though 80 to 90% of cases are considered mild, usually starts a sequence of neurological disorders that can last a considerable time. Most of the research of this injury has been focused on oxidative stress and functional deficits; however, mechanisms that underlie the development of neuropsychiatric disorders remain little researched. Due to this, the present authors decided to investigate whether recurrent concussion protocols alter depressive-like phenotype behavior, and whether mitochondria play an indispensable role in this behavior or not. The experimental data revealed, for the first time, that the present protocol of recurrent concussions (4, 7, and 10 injuries) in mice did not alter immobility time during tail suspension tests (TSTs), but decreased hippocampal mitochondrial respiration and increased expression of proteins such as nuclear factor erythroid 2-related factor 2 (Nrf2) and superoxide (SOD2). This experimental data suggests that bioenergetic changes elicited by recurrent concussion did not induce depressive-like behavior, but activated the transcription factor of responsive antioxidant elements (ARE) that delay or prevent secondary cascades in this neurological disease.

Apoptotic Markers Are Increased in Epilepsy Patients: A Relation with Manganese Superoxide Dismutase Ala16Val Polymorphism and Seizure Type through IL-1ß and IL-6 Pathways.

The MnSOD Ala16Val single nucleotide polymorphism (SNP) has been associated with different diseases. However, there are scarcely studies relating this SNP in epilepsy, a neurologic disease that involves some interacting pathways, such as apoptotic and inflammatory factors. In this sense, we decided to investigate the relationship of MnSOD Ala16Val SNP with apoptotic markers in epilepsy and its relation with inflammatory pathway and seizure type. Ninety subjects were evaluated (47 epilepsies; 43 controls) by questionnaires and laboratorial exams. We observed a higher percentage of VV genotype in the epilepsy group when compared to the control group. IL-1ß, IL-6, caspase-1, and caspase-3 levels were increased in the epilepsy group (VV genotype). Furthermore, an important correlation between IL-1ß vs. caspase-1 and IL-6 vs. caspase-3 was observed in the epilepsy group (VV genotype). The epilepsy group which presented generalized seizures also demonstrated a positive correlation between IL-1ß vs. CASP1 and IL-6 vs. CASP3. Thus, it is a plausible propose that epilepsy patients with VV genotype and generalized seizures present a worse inflammatory and apoptotic status. Our findings suggest that the knowledge of MnSOD Ala16Val polymorphism existence is important to evaluate molecular mechanisms associated to seizure and improve the treatment of these patients.

Course and prognosis of adult-onset epilepsy in Brazil: A cohort study.

BACKGROUND: Most of the epilepsy longitudinal studies have analyzed children. However, in endemic regions, such as Brazil, neurocysticercosis accounts for many adult-onset epilepsy cases. So, the main objective of this study was to identify the clinical predictors associated with drug-resistant adult-onset epilepsy in Brazil during a long-term follow-up. METHODS: We followed 302 individuals with adult-onset epilepsy for 9.8 years in our University Hospital. Structured questionnaires about drug-resistant epilepsy were applied. The presence of drug-resistant epilepsy was the primary outcome. We used multilevel linear modeling in our data analysis. RESULTS: Overall 47 (15.6%) individuals presented drug-resistant epilepsy and the etiology was structural in 70.2% of them, while infectious etiology was present in 8.5% of this group. Infectious etiology occurred in 25.9% (n = 66) of the patients from the nondrug-resistant group. Those with developmental delay were two times more likely to present seizures. Structural epilepsy etiology was associated with an increased chance of relapsing. Poor school performance and abnormal electroencephalogram were also associated with an increased chance of seizures. CONCLUSION: The course of epilepsy was favorable in the majority of our patients, and drug-resistant epilepsy rates were similar to those found in other studies, although we evaluated older individuals with higher levels of infectious etiology. Also, we found that neurocysticercosis was associated with well-controlled epilepsy, while structural epilepsy was directly related to the occurrence of seizures. We also hypothesized that the smaller size of lesions found in neurocysticercosis could contribute to better treatment response.

Neuroprotective effects of thromboxane receptor antagonist SQ 29,548 after pilocarpine-induced status epilepticus in mice.

Thromboxane A2 (TXA2) is an important eicosanoid in the cardiovascular system, and increasing evidence suggests that TXA2 receptors (TPs) and their ligands may constitute valuable tools for the development of neuroprotective drugs. However, the role of TPs on seizure-induced damage has not been investigated. Therefore, we evaluated the effects of SQ 29,548, a potent and selective TP antagonist-on neuromotor performance, neurodegeneration, reactive astrocytosis, and c-Fos protein immunoreactivity after pilocarpine-induced status epilepticus (SE) in mice. Adult C57BL/6 mice received intracerebroventricular SQ 29,548 injections 90 min and 24 h after pilocarpine-induced SE. We found that SQ 29,548 prevented the impairment of neuromotor performance (Neuroscore test) 48 h after pilocarpine-induced SE. Data analysis suggested the existence of two subgroups of SQ 29,548-treated post-SE animals. Eight out of 12 SQ 29,548-treated animals displayed Neuroscore values identical to those of vehicle-treated controls, and were considered SQ 29,548 responders. However, 4 out of 12 SQ 29,548-treated animals did not show any improvement in Neuroscore values, and were considered SQ 29,548 non-responders. Treatment with SQ 29,548 attenuated SE-induced increase in the number of FJC- or GFAP-positive cells in the hippocampus of SQ 29,548 responders. In addition, SQ 29,548 prevented the SE-elicited increase of c-Fos immunoreactivity in the hippocampus. In summary, our results suggest that the TP antagonist (SQ 29,548) improves neurological outcome after pilocarpine-induced SE in mice. The existence of SQ 29,548 responders and non-responders was suggested by results from the Neuroscore test. Additional studies are needed to understand the mechanisms underlying these findings, as well as the potential uses of TP antagonists in the treatment of seizure-induced damage.

Potential therapeutic implications of ergogenic compounds on pathophysiology induced by traumatic brain injury: A narrative review.

Traumatic brain injury (TBI) is a devastating condition that often triggers a sequel of neurological disorders that can last throughout lifespan. From a metabolic viewpoint, the compromising of the energy metabolism of the brain has produced evidence linking the severity of brain injury to the extent of disturbances in the cerebral metabolism. The cerebral metabolic crisis, however, displays that regional heterogeneity varies temporally post-injury. It is important to note that energy generation and mitochondrial function are closely related and interconnected with delayed secondary manifestations of brain injury, including early neuromotor dysfunction, cognitive impairment, and post-traumatic epilepsy (PTE). Given the extent of post-traumatic changes in neuronal function and the possibility of amplifying secondary cascades, different therapies designed to minimize damage and retain/restore cellular function after TBI are currently being studied. One of the possible strategies may be the inclusion of ergogenic compounds, which is a class of supplements that typically includes ingredients used by athletes to enhance their performance. The combination of these compounds offers specific physiological advantages, which include enhanced energy availability/metabolism and improved buffering capacity. However, the literature on their effects in certain biological systems and neurological diseases, such as TBI, has yet to be determined. Thus, the present review aims to discuss the role of ergogenic compounds popularly used in secondary damage induced by this neurological injury. In this narrative review, we also discuss how the results from animal studies can be applied to TBI clinical settings.