Cerebral venous congestion alters brain metabolite profiles, impairing cognitive function

Abstract

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.

Cerebral venous congestion alters CNS homeostatic plasticity, evoking tinnitus-like behavior

“…After the successful establishment of a validated rat model of cerebral venous congestion by JVL [ 5 , 6 , 16 , 17 ], behavioral tests were assessed before surgery as well as 7 days/14 days/1 month/3 months postoperatively (Fig. 1 a).…”

“…When confronted with continuous damage, similar to other systems in the organism, the function of the cerebrovascular system becomes decompensated, ultimately leading to increased energy requirements and further dysregulation of neurovascular and neurometabolic coupling function. Our previous studies have revealed that cerebral venous congestion can provoke brain metabolite profile alterations in response to CBF change and cerebral hypoperfusion [ 16 ]. Accordingly, we speculate that after transient ischemia and hypoxia in the brain, neurons are capable of making homeostatic changes to sustain their steady state and maintain the normal features of the CNS.…”

“…JVL model was generated as previously reported [ 16 , 17 ]. Briefly, rats were deeply anesthetized with 4% isoflurane and subsequently maintained between 1.5 and 2% isoflurane during the surgical procedure using an isoflurane vaporizer (RWD, Shenzhen, China).…”

VICTR: Venous transit time imaging by changes in T1 relaxation

“…Moreover, cerebral venous stenosis and thrombosis can also result in an alteration of VTT and have been suggested to increase the risk of hemorrhagic conversion in stroke patients 24,25 . Cerebral venous congestion has also been suggested to impair cognitive function 26 . The measurement of VTT, therefore, opens several research avenues in understanding vascular function in the normal and pathological brain.…”