Neurochemical research
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Neurochemical research · Jun 2015
Activation of mGluR5 Attenuates Microglial Activation and Neuronal Apoptosis in Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats.
Activation of metabotropic glutamate receptor 5 (mGluR5) provided neuroprotection in multiple central nervous system injury, but the roles of mGluR5 in subarachnoid hemorrhage (SAH) remain unclear. In present study, we aimed to evaluate whether activation of mGluR5 attenuates early brain injury (EBI) after experimental SAH in rats. We found that selective mGluR5 orthosteric agonist CHPG or positive allosteric modulator VU0360172 administration significantly improves neurological function and attenuates brain edema at 24 h after SAH. ⋯ Moreover, CHPG or VU0360172 administration obviously reduces the number of TUNEL-positive cells and active caspase-3/NeuN-positive neurons in cortex at 24 h after SAH. CHPG or VU0360172 administration significantly up-regulates the expression of Bcl-2, and down-regulates the expression of Bax and active caspase-3, which in turn increases the ratio of Bcl-2/Bax. Our results indicate that activation of mGluR5 attenuates microglial activation and neuronal apoptosis, and improves neurological function in EBI after SAH.
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Neurochemical research · Jun 2015
Upregulation of α₂δ-1 Calcium Channel Subunit in the Spinal Cord Contributes to Pelvic Organ Cross-Sensitization in a Rat Model of Experimentally-Induced Endometriosis.
Pelvic organ cross-sensitization, also termed as viscero-visceral referred hyperalgesia, is a major contributor to painful endometriosis. Its underlying mechanism is poorly understood. Clinical and basic studies have shown that gabapentin, a drug that binds to the α2δ-1 subunit of voltage-dependent calcium channels (Cavα2δ-1), is effective in treating chronic visceral pain. ⋯ Furthermore, intrathecal injection of Cavα2δ-1 antisense oligodeoxynucleotides reversed the ectopic growths-to-colon cross-sensitization and also normalized the upregulation of spinal Cavα2δ-1 expression in endometriosis rats. The current study suggests that the upregulation of Cavα2δ-1 in the spinal cord may contribute to pelvic organ cross-sensitization in painful endometriosis. Our study may provide a biological basis for selectively targeting this pathway to relieve viscero-visceral referred hyperalgesia in patients with painful endometriosis.