Rifampicin ameliorates lithium-pilocarpine-induced seizures, consequent hippocampal damage and memory deficit in rats: Impact on oxidative, inflammatory and apoptotic machineries.

Epilepsy is one of the serious neurological sequelae of bacterial meningitis. Rifampicin, the well-known broad spectrum antibiotic, is clinically used for chemoprophylaxis of meningitis. Besides its antibiotic effects, rifampicin has been proven to be an effective neuroprotective candidate in various experimental models of neurological diseases. In addition, rifampicin was found to have promising antioxidant, anti-inflammatory and anti-apoptotic effects. Herein, we investigated the anticonvulsant effect of rifampicin at experimental meningitis dose (20 mg/kg, i.p.) using lithium-pilocarpine model of status epilepticus (SE) in rats. Additionally, we studied the effect of rifampicin on seizure induced histopathological, neurochemical and behavioral abnormalities. Our study showed that rifampicin pretreatment attenuated seizure activity and the resulting hippocampal insults marked by hematoxylin and eosin. Markers of oxidative stress, neuroinflammation and apoptosis were evaluated, in the hippocampus, 24 h after SE induction. We found that rifampicin pretreatment suppressed oxidative stress as indicated by normalized malondialdehyde and glutathione levels. Rifampicin pretreatment attenuated SE-induced neuroinflammation and decreased the hippocampal expression of interleukin-1ß, tumor necrosis factor-α, nuclear factor kappa-B, and cyclooxygenase-2. Moreover, rifampicin mitigated SE-induced neuronal apoptosis as indicated by fewer positive cytochrome c immunostained cells and lower caspase-3 activity in the hippocampus. Furthermore, Morris water maze testing at 7 days after SE induction showed that rifampicin pretreatment can improve cognitive dysfunction. Therefore, rifampicin, currently used in the management of meningitis, has a potential additional advantage of ameliorating its epileptic sequelae.

Huntington's Disease in Arab Countries.

Huntington's disease (HD) is an inherited neurodegenerative disorder. Involuntary choreaform movements are the main symptom. The prevalence of HD in Arab countries is not fully understood, as there are only a few reports indicating disease incidence. Therefore, there is an urgent need for an investigation to determine the frequency of HD in the Middle East, especially within Arab countries, and at the same time enhance people's awareness of the disease.

The anti-apoptotic and anti-inflammatory properties of puerarin attenuate 3-nitropropionic-acid induced neurotoxicity in rats.

Puerarin (Pur), an isoflavonoid extracted from the dried roots of Pueraria lobata, has been reported to be useful in the treatment of various diseases. This study was designed to evaluate the anti-apoptotic and anti-inflammatory activities of Pur against 3-nitropropionic acid (3-NP) induced neurotoxicity. For 5 consecutive days, male Wistar rats were given Pur (200 mg/kg body mass) 30 min before treatment with 20 mg/kg body mass of 3-NP. The striata, hippocampi, and cortices of the 3-NP treated group showed apoptotic damage, inflammation, and energy deficit as well as histopathological lesions. The 3-NP-induced alteration in apoptotic biomarkers (caspase-3 activity/level, cytosolic cytochrome c, Bax/Bcl-2 levels) were significantly ameliorated by Pur treatment. Moreover, Pur pretreatment blocked 3-NP-induced inflammatory biomarkers (NF-κB, TNF-α, and iNOS) and prevented the energy deficit (ATP reduction). Nissl staining further confirmed Pur's neuroprotective effect. These results indicate that Pur may be a useful preventive approach to various neurodegenerative diseases with underlying apoptosis and neuroinflammation.

Puerarin ameliorates 3-nitropropionic acid-induced neurotoxicity in rats: possible neuromodulation and antioxidant mechanisms.

Puerarin (daidzein-8-C-glucoside), a major isoflavone glycoside purified from Pueraria lobata, is well reported to have a neuroprotective effect primarily by the antioxidant mechanisms. This investigation was designed to evaluate the efficacy of Puerarin (Pur) to offset 3-nitropropionic acid (3-NP) induced neurotoxicity. Male Wistar strain rats were given 3-NP (20 mg/kg, s.c.) over five consecutive days, whereas Pur (200 mg/kg, i.p.) was administrated 30 min before 3-NP. Rats treated with 3-NP exhibited significant weight loss, reduction of the prepulse inhibition, locomotor hypoactivity and hypothermia. The striata, hippocampi and cortices of the 3-NP treated rats showed abnormal levels of neurotransmitters, oxidative damage and characteristic histopathological lesions. Treatment with Pur ahead of 3-NP, significantly prevented weight loss, PPI deficit, locomotor hypoactivity and hypothermia. Pur treatment blocked the 3-NP-induced neurotransmitters abnormalities (GABA, DA, 5-HT and NE), and normalized the oxidative stress biomarkers (lipid peroxidation, reduced glutathione, glutathione peroxidase). Histopathological examination further affirmed Pur's neuroprotective effect against 3-NP-induced neurotoxicity. In conclusion, Pur protected the brain tissues from 3-NP induced neurotoxicity primarily by its neuromodulation and antioxidant effect.

The effect of Ginkgo biloba extract on 3-nitropropionic acid-induced neurotoxicity in rats.

3-Nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase enzyme (SDH), induces neurodegeneration similar to that observed in Huntington's disease (HD). Reduction of prepulse inhibition (PPI) of acoustic startle response, locomotor hypoactivity, bilateral striatal lesions as well as brain oxidative stress are major features of HD. The present study was designed to investigate neuroprotective effect of Ginkgo biloba extract (EGb 761) on 3-NP induced neurobehavioral changes and striatal lesions. Rats administered 3-NP (20mg/kg, s.c.) for five consecutive days exhibited PPI deficits and locomotor hypoactivity whereas, pretreatment of animals with EGb 761 (100mg/kg, i.p. for 15 days) ahead of and during the induction of HD by 3-NP (20mg/kg for 5 days starting at day 8) ameliorated 3-NP-induced neurobehavioral deficits. Administration of 3-NP increased the level of striatal malondialdehyde (MDA). This effect was prevented in animals pre-treated with EGb 761. Changes in the level of apoptotic regulatory gene expressions, following 3-NP treatment, were demonstrated as both an up-regulation and a down-regulation of the expression levels of striatal Bax and Bcl-xl genes, respectively. In addition, an up-regulation of the expression level of striatal glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was also observed. Pre-treatment with EGb 761 caused a down-regulation in striatal GAPDH and Bax together with an up-regulation of striatal Bcl-xl expression level as compared to the 3-NP treated group. Histochemical examination of striatal tissue showed that EGb 761 significantly prevented 3-NP induced inhibition of SDH activity. Histopathological examination further affirmed the neuroprotective effect of EGb 761 against 3-NP toxicity. Taken together, these results suggest that EGb 761 has a neuroprotective role in the current HD paradigm, which may be related to improvement of energy metabolism, antioxidant properties and antiapoptotic effects.