Cerebral Microcirculation and Histological Mapping After Severe Head Injury: A Contusion and Acceleration Experimental Model.

Judith Bellapart,David G Platts,Levon Gabrielian,Jenifer Paratz,Owen Christopher Raffel,John F Fraser,Adrian Barnett,Sara Diab,Kimble Dunster,Rob Boots,Kylie Cuthbertson

doi:10.3389/fneur.2018.00277

Abstract

Cerebral microcirculation after severe head injury is heterogeneous and temporally variable. Microcirculation is dependent upon the severity of injury, and it is unclear how histology relates to cerebral regional blood flow. This study assesses the changes of cerebral microcirculation blood flow over time after an experimental brain injury model in sheep and contrasts these findings with the histological analysis of the same regions with the aim of mapping cerebral flow and tissue changes after injury. Microcirculation was quantified using flow cytometry of color microspheres injected under intracardiac ultrasound to ensure systemic and homogeneous distribution. Histological analysis used amyloid precursor protein staining as a marker of axonal injury. A mapping of microcirculation and axonal staining was performed using adjacent layers of tissue from the same anatomical area, allowing flow and tissue data to be available from the same anatomical region. A mixed effect regression model assessed microcirculation during 4 h after injury, and those results were then contrasted to the amyloid staining qualitative score. Microcirculation values for each subject and tissue region over time, including baseline, ranged between 20 and 80 ml/100 g/min with means that did not differ statistically from baseline flows. However, microcirculation values for each subject and tissue region were reduced from baseline, although their confidence intervals crossing the horizontal ratio of 1 indicated that such reduction was not statistically significant. Histological analysis demonstrated the presence of moderate and severe score on the amyloid staining throughout both hemispheres. Microcirculation at the ipsilateral and contralateral site of a contusion and the ipsilateral thalamus and medulla showed a consistent decline over time. Our data suggest that after severe head injury, microcirculation in predefined areas of the brain is reduced from baseline with amyloid staining in those areas reflecting the early establishment of axonal injury.

Highlights

Severe head injury is commonly the result of a combination of contusion with acceleration–deceleration forces leading to cellular breakdown, cytogenic and vasogenic edema, impaired cerebral autoregulation, and perfusion mismatch [1]
Despite the previously demonstrated relationship between regional microcirculatory blood flow (RMBF), tissue metabolic demands [5], and cerebral hypoperfusion leading to irreversible cellular damage, there are no studies quantifying the temporal variability of RMBF in different cerebral anatomical regions after severe head injury, its close relation to the degree of tissue damage assessed by amyloid precursor protein (APP) staining or the state of cerebral tissue oxygenation
We hypothesized that after severe head injury cerebral microcirculation heterogeneity may correlate to the severity of the injury with maximal RMBF reduction seen within the areas of severe tissue disruption

Summary

Introduction

Severe head injury is commonly the result of a combination of contusion with acceleration–deceleration forces leading to cellular breakdown, cytogenic and vasogenic edema, impaired cerebral autoregulation, and perfusion mismatch [1]. While the assessment of cerebral regional microcirculation is primordially experimental in nature, its knowledge is essential in comprehending further the pathophysiology behind severe head injury and its extrapolation to clinical grounds. Management of head injury patients is commonly based on systemic measures that ensure global perfusion and oxygenation, without targeting cerebral metabolic demands, cerebral tissue oximetry, or regional distribution of blood flow. Despite the previously demonstrated relationship between regional microcirculatory blood flow (RMBF), tissue metabolic demands [5], and cerebral hypoperfusion leading to irreversible cellular damage, there are no studies quantifying the temporal variability of RMBF in different cerebral anatomical regions after severe head injury, its close relation to the degree of tissue damage assessed by amyloid precursor protein (APP) staining or the state of cerebral tissue oxygenation. Cerebral microcirculation after severe head injury is heterogeneous and temporally variable. Microcirculation is dependent upon the severity of injury, and it is unclear how histology relates to cerebral regional blood flow

Methods

Results

Discussion

Conclusion