Carnosine, an endogenous dipeptide (β-alanyl-L-histidine), exerts multiple neuroprotective properties, but its role in intracerebral hemorrhage (ICH) remains unclear. This study investigates the effect of Carnosine on brain injury using the rat ICH model, which is established by type IV collagenase caudatum infusion. The results indicate that intraperitoneal administration of Carnosine (1000 mg/kg) significantly attenuates brain edema, blood-brain barrier (BBB) disruption, oxidative stress, microglia activation and neuronal apoptosis of perihematoma at 72 h following ICH in rats models, as convinced by preventing the disruption of tight junction protein ZO-1, occludin and claudin-5, followed by the decrease of ROS, MDA, 3-NT, 8-OHDG level and the increase of GSH-Px and SOD activity, then followed by the decline of Iba-1, ED-1, active caspase-3 and TUNEL positive cells and the decrease of IL-1β, IL-6, TNF-α, active caspase-3 and cytochrome c level. Our results suggest that Carnosine may provide neuroprotective effect after experimental ICH in rat models.
Roflumilast, a selective inhibitor for PDE4, is approved by FDA as an anti-inflammation drug for treatment of chronic obstructive pulmonary disease (COPD). This study investigates the effects of roflumilast on cerebral inflammation in the rat SAH model. Here, we show that subcutaneous administration of roflumilast (3 mg/kg) significantly improved the neurological deficits. Measurement of evans blue extravasation and brain water content revealed a significant reduction of blood-brain barrier permeability and brain edema. Importantly, roflumilast treatment remarkably decreased levels of IL-1β, IL-6, and TNF-α and the number of apoptotic neurons in the brain after SAH. These results indicate that roflumilast is effective in treating cerebral inflammation following SAH.
Excessive
glutamate-mediated overactivation of metabotropic glutamate
receptor 1 (mGluR1) plays a leading role in neuronal apoptosis following
subarachnoid hemorrhage (SAH). TAT-mGluR1, a fusion peptide consisting
of a peptide spanning the calpain cleavage site of mGluR1α and
the trans-activating regulatory protein (TAT) of HIV, effectively
blocks mGluR1α truncation and protects neurons against excitotoxic
damage. This study investigated the effects of TAT-mGluR1 on neuronal
apoptosis in the rat SAH model. Here, we report that SAH caused activation
of calpain and truncation of mGluR1α; intraperitoneally administered
TAT-mGluR1 did not affect calpain activity, while it blocked truncation
of mGluR1α after SAH. Intraperitoneally administered FITC-labeled
TAT-mGluR1 was colocalized with mGluR1α in thecortex after SAH.
Furthermore, TAT-mGluR1 significantly improved the neurological deficit,
increased p-PI3K, p-Akt, and p-GSK3β, downregulated Bax, upregulated
Bcl-2, and reduced cortical apoptosis in the basal cortex at 24 h
after SAH. These findings indicated that TAT-mGluR1 acted against
SAH-induced cell apoptosis through preventing mGluR1α truncation.
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