Acute and chronic stage adaptations of vascular architecture and cerebral blood flow in a mouse model of TBI

Abstract

max 200 words):The 3D organization of cerebral blood vessels determines the overall capacity of the cerebral circulation to meet the metabolic requirements of the brain. This study used Arterial Spin Labeling (ASL) MRI with a hypercapnic challenge and ex vivo Serial Two-Photon Tomography (STPT) to examine the relationship between blood flow and 3D microvascular structure following traumatic brain injury (TBI) in a mouse. Mice were exposed to a controlled cortical impact TBI and allowed to recover for either 1 day or 4 weeks. At each time point, ASL MRI was performed to quantify cerebral perfusion and the brain vasculature was imaged in 3D with STPT. Registration of ASL to STPT enabled flow changes to be related to the underlying microvascular structure in each ASL voxel. Hypoperfusion under rest and hypercapnia was observed both 1 day and 4 weeks post-TBI. Vessel density and vascular volume were reduced 1 day post-TBI, recovering by 4 weeks; however, the reorganized vasculature at the latter time point possessed an abnormal radial pattern. Our findings demonstrate functionally significant long-term changes in the vascular architecture following injury and illustrate why metrics beyond traditional measures of vessel density are required to understand the impact of vascular structure on function.

Impairment of cerebrovascular reactivity in response to hypercapnic challenge in a mouse model of repetitive mild traumatic brain injury

“…86,87 Obenaus et al 88 have catalogued an acute rarefaction of global cerebrovascular density at 1 day following mTBI in mice, 88 with a recovery to baseline levels by 14 days post-injury, and Hayward et al 89 have shown acute cerebrovascular loss, before revascularization with persistent hypoperfusion at 14 days post injury in a rat model of TBI. 89 Steinman et al 90 have shown blunted resting and hypercapniainduced CBF at four weeks following CCI in mice, despite recovery of microvascular density and volume detriments recorded at one day post injury. These data not only suggest an acute loss and later return of cerebrovascular density following brain trauma in animal models, and possibly human patients, but also demonstrate that revascularization does not necessarily translate to functional recovery.…”

“…89 Steinman et al. 90 have shown blunted resting and hypercapnia-induced CBF at four weeks following CCI in mice, despite recovery of microvascular density and volume detriments recorded at one day post injury. These data not only suggest an acute loss and later return of cerebrovascular density following brain trauma in animal models, and possibly human patients, but also demonstrate that revascularization does not necessarily translate to functional recovery.…”