Neuronal deterioration associated with hyperexcitability under mild chronic cerebral hypoperfusion

Area of Science:

• Neuroscience
• Cerebrovascular Medicine
• Neuroimaging

Background:

• Chronic cerebral hypoperfusion (CCH) is linked to cognitive impairment.
• The precise neural mechanisms underlying CCH-induced brain dysfunction are not fully understood.

Purpose of the Study:

• To investigate the impact of CCH on neuronal activity and neurochemical changes.
• To elucidate the role of glutamate and NMDA receptors in CCH-related brain alterations.

Main Methods:

• Induction of unilateral common carotid artery occlusion in male mice.
• Utilized optical imaging and MRI for monitoring neuronal activity.
• Administered pharmacological blockade of NMDA receptors.

Main Results:

• Early CCH (up to 7 days) showed increased neuronal activity, glutamate, and acidosis.
• Later CCH (21-28 days) exhibited decreased neuronal activity with persistent acidosis.
• Early NMDA receptor blockade prevented hyperexcitation and subsequent neuronal deficits.

Conclusions:

• CCH initially causes glutamate surge and neuronal hyperexcitation.
• This early phase leads to progressive deterioration of neuronal function.
• Targeting NMDA receptors early in CCH may mitigate cognitive decline.