Hypothermia and pharmacological regimens that prevent overexpression and overactivity of the extracellular calcium-sensing receptor protect neurons against traumatic brain injury.

摘要: Traumatic brain injury (TBI) leads to acute functional deficit in the brain. Molecular events underlying TBI remain unclear. In mouse brains, we found controlled cortical impact (CCI) induced overexpression of extracellular calcium-sensing receptor (CaSR), which is known stimulate neuronal activity and accumulation intracellular Ca(2+) concurrent down-regulation type B or metabotropic GABA 1 (GABA-B-R1), a prominent inhibitory pathway These changes protein expression preceded were closely associated with loss tissue, as indicated by increased size cavity at sites, development motor deficit, frequency right-biased swing turn CCI mice. Mild hypothermia, an established practice neuroprotection for ischemia, partially but significantly blunted all above effects CCI. Administration CaSR antagonist NPS89636 mimicked hypothermia reduce tissue functions data together support concept that overactivity play causal role potentiating potentially stimulating excitatory responses interfering GABA-B-R signaling could be novel target against TBI.