Cerebral venous congestion alters brain metabolite profiles, impairing cognitive function.
Huimin WeiHuimin JiangYifan ZhouXuechun XiaoChen ZhouXun-Ming JiPublished in: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (2023)
Vascular cognitive impairment (VCI) represents the second most common cause of dementia after Alzheimer's disease, and pathological changes in cerebral vascular structure and function are pivotal causes of VCI. Cognitive impairment caused by arterial ischemia has been extensively studied the whole time; the influence of cerebral venous congestion on cognitive impairment draws doctors' attention in recent clinical practice, but the underlying neuropathophysiological alterations are not completely understood. This study elucidated the specific pathogenetic role of cerebral venous congestion in cognitive-behavioral deterioration and possible electrophysiological mechanisms. Using cerebral venous congestion rat models, we found these rats exhibited decreased long-term potentiation (LTP) in the hippocampal dentate gyrus and impaired spatial learning and memory. Based on untargeted metabolomics, N-acetyl-L-cysteine (NAC) deficiency was detected in cerebral venous congestion rats; supplementation with NAC appeared to ameliorate synaptic deficits, rescue impaired LTP, and mitigate cognitive impairment. In a cohort of cerebral venous congestion patients, NAC levels were decreased; NAC concentration was negatively correlated with subjective cognitive decline (SCD) score but positively correlated with mini-mental state examination (MMSE) score. These findings provide a new perspective on cognitive impairment and support further exploration of NAC as a therapeutic target for the prevention and treatment of VCI.
Keyphrases
- cognitive impairment
- subarachnoid hemorrhage
- cognitive decline
- transcription factor
- cerebral ischemia
- mild cognitive impairment
- mass spectrometry
- clinical practice
- brain injury
- newly diagnosed
- mental health
- cerebral blood flow
- resting state
- depressive symptoms
- traumatic brain injury
- combination therapy
- multiple sclerosis
- patient reported outcomes