Buyang Huanwu Decoction alleviates cerebral ischemic injury through modulating caveolin-1-mediated mitochondrial quality control.

Introduction: Mitochondrial quality control (MQC) is an important mechanism of neural repair after cerebral ischemia (CI). Recent studies have shown that caveolin-1 (Cav-1) is an important signaling molecule in the process of CI injury, but its mechanism of regulating MQC after CI is still unclear. Buyang Huanwu Decoction (BHD) is a classic traditional Chinese medicine formula that is often used to treat CI. Unfortunately, its mechanism of action is still obscure. Methods: In this study, we tested the hypothesis that BHD can regulate MQC through Cav-1 and exert an anti-cerebral ischemia injury effect. We used Cav-1 knockout mice and their homologous wild-type mice, replicated middle cerebral artery occlusion (MCAO) model and BHD intervention. Neurobehavioral scores and pathological detection were used to evaluate neurological function and neuron damage, transmission electron microscopy and enzymology detection of mitochondrial damage. Finally, western blot and RT-qPCR expression of MQC-related molecules were tested. Results: After CI, mice showed neurologic impairment, neuronal damage, and significant destruction of mitochondrial morphology and function, and MQC was imbalanced. Cav-1 deletion aggravated the damage to neurological function, neurons, mitochondrial morphology and mitochondrial function after CI, aggravated the imbalance of mitochondrial dynamics, and inhibited mitophagy and biosynthesis. BHD can maintain MQC homeostasis after CI through Cav-1 and improve CI injury. Discussion: Cav-1 can affect CI injury by regulating MQC, and this mechanism may be another target of BHD for anti-cerebral ischemia injury.

Upregulation and Diverse Roles of TRPC3 and TRPC6 in Synaptic Reorganization of the Mossy Fiber Pathway in Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is the most common form of intractable epilepsy and is always accompanied with hippocampal sclerosis. The molecular mechanism of this pathological phenomenon has been extensively explored, yet remains unclear. Previous studies suggest that ion channels, especially calcium channels, might play important roles. Transient receptor potential canonical channel (TRPC) is a novel cation channel dominantly permeable to Ca(2+) and widely expressed in the human brain. We measured the expression of two subtypes of TRPC channels, TRPC3 and TRPC6, in temporal lobe epileptic foci excised from patients with intractable epilepsy and in hippocampus of mice with pilocarpine-induced status epilepticus (SE), an animal model of TLE. Cortical TRPC3 and TRPC6 protein expressions were significantly higher in TLE patients compared with those in controls. Expression of TRPC3 and TRPC6 protein also increased significantly in the CA3 region of the hippocampus of SE mice. Inhibition of TRPC3 by intracerebroventricular injection of anti-TRPC3 antibody prevented aberrant-sprouted mossy fiber collaterals in the CA3 region, while inhibition of TRPC6 by anti-TRPC6 antibody reduced dendritic arborization and spine density of CA3 pyramidal neurons. Our results indicate that TRPC3 and TRPC6 participate diversely in synaptic reorganization in the mossy fiber pathway in TLE.

Altered expression of pannexin proteins in patients with temporal lobe epilepsy.

The aim of the present study was to investigate the expression of the pannexin (Panx) proteins, Panx1 and Panx2, in the temporal lobe tissue of patients with temporal lobe epilepsy (TLE). Immunohistochemistry and western blotting methods were used to localize and quantify Panx1 and Panx2 in the surgically removed brain tissue of patients with TLE (n=37). The results were then compared with non-epileptogenic controls (n=9). Panx1 and Panx2 expression was detected in the temporal lobe cortex of patients with TLE and in the control tissues. Panx1 and Panx2 proteins were expressed in all layers of the epileptic cortex, but predominantly in layers II and III of the cortex in the control group. Panx1 protein expression was significantly higher in the temporal lobe cortex of the patients with TLE than in the controls (P<0.05; t-test); however, no significant differences were identified in the Panx2 expression levels between the patients and the controls (P>0.05; t-test). The expression of the two Panx proteins in the tissue layers of the epileptic cortex varied in the patients and controls. The results indicate that Panx channels may be involved in the pathogenesis of TLE.