Article
Modulation of neuronal network disinhibition in treatment of spreading depression-related brain disorders
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Published: | June 9, 2017 |
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Objective: Spreading depression (SD), a slow propagating depolarisation wave, is followed by alterations in cellular and synaptic hyperexcitability of the brain and is involved in the pathophysiology of several brain disorders, such as subarachnoid hemorrhage and traumatic brain injury. Disinhibition of GABA function is involved in the late hyperexcitability state of SD. The aim of the present study was to evaluate the role of modulation of GABA function on SD-induced neuronal network disinhibition.
Methods: The effect of KCl-induced negative DC deflections was studied on paired-pulse depression (PPD) as well as intracellularly recorded inhibitory post synaptic potentials (IPSPs). Furthermore, the role of gabapentin was investigated on SD-induced neuronal network disinhibition.
Results: SD inhibited the degree of PPD and decreased the amplitude and duration of IPSPs. Administration low concentrations of bicuculline before SD induction increased the inhibitory effect of SD on IPSPs. Gabapentin prevented the inhibitory effect of SD on IPSPs.
Conclusion: Modulation of SD-induced neuronal network disinhibition in the late hyperexcitability state of SD may play a role in therapeutic management of SD-related brain disorders.