No abstract

Asiatic acid, a triterpenoid derivative from Centella asiatica, has shown biological effects such as antioxidant, antiinflammatory, and protection against glutamate-or β-amyloid-induced neurotoxicity. We investigated the neuroprotective effect of asiatic acid in a mouse model of permanent cerebral ischemia. Various doses of asiatic acid (30, 75, or 165 mg/kg) were administered orally at 1 hr pre-and 3, 10, and 20 hr postischemia, and infarct volume and behavioral deficits were evaluated at day 1 or 7 postischemia. IgG (blood-brain barrier integrity) and cytochrome c (apoptosis) immunostaining was carried out at 24 hr postischemia. The effect of asiatic acid on stress-induced cytochrome c release was examined in isolated mitochondrial fractions. Furthermore, its effects on cell viability and mitochondrial membrane potential were studied in HT-22 cells exposed to oxygenglucose deprivation. Asiatic acid significantly reduced the infarct volume by 60% at day 1 and by 26% at day 7 postischemia and improved neurological outcome at 24 hr postischemia. Our studies also showed that the neuroprotective properties of asiatic acid might be mediated in part through decreased blood-brain barrier permeability and reduction in mitochondrial injury. The present study suggests that asiatic acid may be useful in the treatment of cerebral ischemia.Keywords infarct volume; blood-brain barrier; oxygen-glucose deprivation; mitochondria; apoptosis Although the molecular mechanisms involved in ischemic brain injury are not fully understood, much progress has been made in identifying some pathogenic pathways, such as inflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress, that might be involved in ischemic neuronal death (Durukan and Tatlisumak, 2007 Centella asiatica is a herbaceous plant that might also have medicinal value. It is being used in Ayurvedic preparations to improve learning and memory (Zheng and Qin, 2007). Published data suggest that the plant extract has nootropic effects (Rao et al., 2005), protects the brain from age-related oxidative damage (Subathra et al., 2005), and promotes nerve growth and neuronal dendritic arborization (Mohandas et al., 2006).Asiatic acid (AA), a pentacyclic triterpene derivative from Centella asiatica, has been shown to display neuroprotective properties both in vitro and in vivo (Bonfill et al., 2006). In cellular systems, AA was reported to offer protection against β-amyloid-induced cell death in the neuroblastoma B103 cell line (Mook-Jung et al., 1999;Jew et al., 2000). It also reduced H 2 O 2 -related cell death and decreased intracellular free radical concentration (Mook-Jung et al., 1999). Furthermore, AA derivatives were effective at rescuing primary rat cortical cells from glutamate-induced toxicity through activation of the cellular oxidative defense pathway (Lee et al., 2000).Because AA exhibits numerous pharmacological activities that might be beneficial to the ischemic brain, and given that no significant toxicity was observed following subcutaneous o...

Background and Purpose-Carnosine is a naturally occurring dipeptide with multiple neuroprotective properties. In addition, it is well tolerated in high doses with minimal side effects. The purposes of this study were to determine whether carnosine is neuroprotective in permanent focal cerebral ischemia and to determine potential mechanisms of neuroprotection. Methods-We investigated the efficacy of carnosine in a mouse model of permanent focal cerebral ischemia. The effects of carnosine were investigated with respect to neuronal damage and infarct formation, endogenous antioxidant status, and matrix metalloproteinase activity. Results-Carnosine significantly decreased infarct size and neuronal damage when administered at time points both before and after the induction of ischemia. Carnosine also decreased reactive oxygen species levels in the ischemic brain, preserved normal glutathione levels, and decreased matrix metalloproteinase protein levels and activity. Conclusions-Carnosine is neuroprotective in focal cerebral ischemia and appears to influence deleterious pathological processes that are activated after the onset of ischemia.

A b s t r a c t

Role of calcium ion (Ca2+) in the functioning of neurons from their naïve state to mature state is of vital importance. It controls functions such as neuronal functioning, neuronal ATP production, central nervous system migration and many others. Failure in Ca2+ homeostasis mechanisms and the resulting cellular Ca2+ ion load initiates a cascade of reactions involving various cytosolic enzymes and proteins. This total mechanism leads to the neuronal death. The ability of neurons to resist such death mechanisms fails as a result of extensive cell death signaling cascade reactions and later brings brain damage. The role of neuronal endoplasmic reticulum and protein channels like CaVs, TRP channels, and NMDAR as the mediators of cell damage and death has been evaluated in the studies related to cerebral ischemia. Here, we portray Ca2+ ion as one of the role players in neuronal death and cerebral damage following ischemia. The role of Ca2+ in neuronal functioning, its regulatory mechanisms and the failure of homeostatic mechanisms are discussed in detail.