The role of HCN channels in early brain injury after SAH

ZHAO Tong; LI Bo; YUAN Shaoji; LU Peigang

Abstract：Objective The role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in early brain injury after subarachnoid hemorrhage (SAH) was discussed and evaluated.Methods SAH models (the arterial puncture model) in Wistar rats were established and divided into four groups with 5 rats in each including Sham group,SAH +vehicle group,SAH + ZD7288 group,and SAH + NO/Spermine (NO/Sp) group.SAH Grading and neurological examination (Modified Garcia) were performed at 24 h after SAH in different groups.Cell death detection were performed at 24 h after SAH in different groups.Assessment of cerebrospinal fluid (CSF) and Glutamic acid (Glu) concentration were performed at 24 h after SAH in different groups.Results 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.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 change for neuronal apoptosis between SAH and NO/Sp-treament groups.Inhibition of HCN channel by ZD7288 had a trend of increasing the Glu concentration in CSF at 24 h after SAH.Conclusion 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;however,giving HCN channels nonspecific agonists does not significantly improve this (the neuronal damage and neurological damage) situation.So this still needs further experimental research.