Abstract
Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality. The mechanisms underlying its pathological complications have not been fully identified. Here, we investigate the potential involvement of the glymphatic system in the neuropathology of SAH. We demonstrate that blood components rapidly enter the paravascular space following SAH and penetrate into the perivascular parenchyma throughout the brain, causing disastrous events such as cerebral vasospasm, delayed cerebral ischemia, microcirculation dysfunction and widespread perivascular neuroinflammation. Clearance of the paravascular pathway with tissue-type plasminogen activator ameliorates the behavioral deficits and alleviates histological injury of SAH. Interestingly, AQP4−/− mice showed no improvements in neurological deficits and neuroinflammation at day 7 after SAH compared with WT control mice. In conclusion, our study proves that the paravascular pathway dynamically mediates the pathological complications following acute SAH independently of glymphatic control.
Highlights
Previous studies have shown that the blockade of cerebral lymphatic drainage deteriorated the secondary cerebral ischemia after subarachnoid hemorrhage (SAH), suggesting that the cerebral lymphatic drainage pathway could be involved in the pathological mechanism of SAH.[10,11] the central nervous system (CNS) was considered lack of a conventional lymphatic drainage system in the past
Using unenhanced computed tomography (CT) scan, CT angiography (CTA) and contrast-enhanced CT scan, we found the high-density areas were almost overlapped on these CT scan images in a set of SAH patients (Figure 6a), suggesting that the ferritin accumulation occurs along the blood vessels following SAH
delayed cerebral ischemia (DCI) is an important cause for poor prognosis of SAH.[2]
Summary
Previous studies have shown that the blockade of cerebral lymphatic drainage deteriorated the secondary cerebral ischemia after SAH, suggesting that the cerebral lymphatic drainage pathway could be involved in the pathological mechanism of SAH.[10,11] the central nervous system (CNS) was considered lack of a conventional lymphatic drainage system in the past. Brain imaging study with magnetic resonance imaging reported weakened GS perfusion following acute stroke or SAH.[18,20] little is known about whether the GS is involved in the secondary complications of SAH. We examined the potential involvement of GS in SAHassociated pathology progression with in vivo two-photon microscopy and CLARITY technique.[21,22] Our data showed that subarachnoid blood flowed into the brain parenchyma rapidly through the PVS, causing CVS, vasculitis, widespread
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