Effect of Alcohol on Diffuse Axonal Injury in Rat Brainstem: Diffusion Tensor Imaging and Aquaporin-4 Expression Study

Abstract

The aim of this study is to assess the effects of alcohol on traumatic brain injury by using diffusion tensor imaging (DTI) and evaluate aquaporin-4(AQP4) expression changes in rat brainstems following acute alcohol intoxication with diffuse axonal injury (DAI). We further investigated the correlation between the AQP4 expression and DTI in the brain edema. Eighty-five rats were imaged before and after injury at various stages. DTI was used to measure brainstem apparent diffusion coefficient (ADC) and fractional anisotropy (FA), with immunostaining being used to determine AQP4 expression. After acute alcoholism with DAI, ADC values of the brainstem first decreased within 6 h and then elevated. FA values began to decline by 1 h, reaching a minimum at 24 h after trauma. There was a negative correlation between ADC values and brainstem AQP4 expression at 6 h and positive correlation at 6 h to 24 h. Changes of ADC and FA values in DAI with acute alcoholism indicate the effects of ethanol on brain edema and the severity of axonal injury. The correlations between ADC values and the brainstem AQP4 expression at different time points suggest that AQP4 expression follows an adaptative profile to the severity of brain edema.

Molecular Neuropathology of Astrocytes and Oligodendrocytes in Alcohol Use Disorders

“…Effects of alcohol mediated by astrocytes very likely involve changes in aquaporins as well (Kong et al, 2013 ), in particular aquaporin 4 (AQ4), a membrane protein highly expressed in astrocytes processes at the BBB that allows effective passage of water through the cell membrane (Badaut et al, 2002 ; Rajkowska et al, 2013 ). Repeated alcohol intake in binging rat models results in significant increases in aquaporin, astrocyte swelling (linked to brain edema) and activation of neuroinflammatory cascades (Collins and Neafsey, 2012 ; Collins et al, 2013 ).…”

Ethanol and isolated traumatic brain injury

“…The systemic catecholamine surge following TBI which is associated with worse outcomes has been shown to be moderated by ethanol [14][15][16]. Aquaporin-4, implicated in the development of cerebral oedema following TBI, has also been shown to be suppressed by ethanol [17]. A further neuroprotective mechanism may be the reduction of hyperglycolysis associated with ethanol exposure following TBI [10].…”

Diffusion Tensor Imaging-Based Studies at the Group-Level Applied to Animal Models of Neurodegenerative Diseases

“…In particular, DTI has revealed the beneficial effect on white matter integrity of activation of mitochondrial calcium fluxes (Parent et al, 2020 ), of autophagy modulators (Medina et al, 2017 ; Yin et al, 2018 ), estrogens (Kim et al, 2015 , 2017 ), metamphetamine (Ding et al, 2013 ), erythropoietin (Robinson et al, 2016 , 2018 ), tissue plasminogen activator (in mice; Xia et al, 2018 ), mGluR5 (in mice; Byrnes et al, 2012 ), and dietary modulations (Shultz et al, 2015 ; Schober et al, 2016 ; Tan et al, 2016 ). Notably, the detrimental effect of alcohol in TBI was also investigated by DTI (Kong et al, 2013 ). Taken together, these studies extensively highlight the sensitivity of DTI as readout of acute and subacute axonal damage in rodents TBI models.…”