The Role Of HCN Channels In Early Brain Injury After SAH

ObjectiveTo observe and evaluate the role of hyperpolarization-activated cyclic nucleotidegated(HCN)channels in early brain injury after subarachnoid hemorrhage(SAH)and further confirm the role of HCN channels in early brain injury after SAH.Methods1.After establishment of SAH modle(The arterial puncture model)in Wiatar rats,they were divided into four groups of 5 animals each,i.e.Sham;SAH+Vehicle;SAH + ZD7288;SAH + NO/Spermine(NO/Sp).2.Ventriculus lateralis cerebri microinjection:in the later two groups,ZD7288 and NO/Spermine(NO/Sp)were injected into the lateral ventricles of the brain respectively.3.SAH Grading and Neurological examination(Modified Garcia)were performed at 24 h after SAH in different groups.4.Cell death detection were performed at 24 h after SAH in different groups.Assessment of cerebrospinal fluid(CSF).5.Glutamic acid(Glu)concentration were performed at 24 h after SAH in different groups.Results1.SAH Grading and Neurological examination(Modified Garcia): Inhibition of HCN channel further aggravated neurological impairment at 24 h after SAH.However unfortunately,there was no amelioration for neurological function after the treatment of NO/Sp.2.Cell death detection :Neurons apoptosis in hippocampus and medial prefrontal cortex(mPFC)was observed at 24 h after SAH,especially in hippocampus.Inhibition of HCN channel by ZD7288 increased the amount of neuronal apoptosis at 24 h after SAH.However,there was no changes for neuronal apoptosis between SAH and NO/Sptreament group.3.Glutamic acid(Glu)concentration :Inhibition of HCN channel by ZD7288 had a trend of increasing the Glu concentration in CSF at 24 h after SAH.Conclusion1.HCN channels play an important role in early brain injury after SAH,neuronal excitability disorders caused by its function cut will directly result in the neuronal damage and eventually lead to nerve function damage after SAH.Inhibition of HCN channels will promote the vicious cycle,further aggravate the neuronal damage and neurological deficits;2.however,giving HCN channels nonspecific agonists did not significantly improve this(the neuronal damage and neurological damage)situation,this is still need further experimental research.