Cortical-wide impairment of “The Glymphatic system” after focal brain injury

Abstract

In peripheral tissues, cells are maintained in the interstitial fluid that flows from capillaries to lymph system. However, the brain has no lymphatic capillaries, and the actual state of the interstitial fluid has long been unknown. Recently, a glymphatic system has been proposed in which part of the cerebrospinal fluid flowing on the surface of brain tissue enters the brain parenchyma via the peri-arterial space, becomes interstitial fluid, and then flows out again from the peri-venous space. Brain injury due to head contusion or stroke is thought to impair the intracerebral circulation and aggravate the extracellular environment, but the actual situation is unknown. Therefore, in this study, we examined the effects of focal brain tissue damage on intracerebral circulation using the light-injured mouse, an originally developed closed head injury model. In light-injured mice, the injury-making process does not affect intracerebral circulation because the cranium is maintained. However, this method has quantitative problems, so we developed a method to image cerebrospinal fluid and blood vessels from the surface of the cerebral cortex. After examining different injury sites and different time periods after injury, it was found that intracerebral circulation was reduced to the same extent on the ipsilateral and contralateral sides of the injury at one-week post-injury. This intracerebral circulatory deficit was still partially present at four-weeks post-injury. These results indicate that the intracerebral circulation is extensively impaired by local injury and neurodegenerative diseases.