Oligodendrocyte Vulnerability Following Traumatic Brain Injury in Rats: Effect of Moderate Hypothermia

Abstract

The purpose of this study was to document patterns of oligodendrocyte vulnerability to TBI and determine whether posttraumatic hypothermia prevents oligodendrocyte cell loss. Sprague Dawley rats underwent moderate fluid percussion brain injury. Thirty minutes after TBI, brain temperature was reduced to 33°C for 4 hrs or maintained at normothermic levels (37°C). Animals were perfusion-fixed for quantitative immunohistochemical analysis at 3 (n=9) or 7 (n=9) days post-TBI. Within the cerebral cortex, external capsule and corpus callosum, numbers of APC-CC1 immunoreactive oligodendrocytes at 3 and 7 days following TBI were significantly decreased compared to sham operated rats (p<0.02). Double-labeling studies showed that vulnerable oligodendrocytes expressed increased Caspase 3 activation compared to sham. Posttraumatic hypothermia significantly reduced the number of CC1 positive oligodendrocytes lost after normothermia TBI in white matter tracts (p<0.01). This model of TBI leads to quantifiable regional patterns of oligodendrocyte vulnerability. Posttraumatic hypothermia protects oligodendrocytes by interfering with Caspase 3-mediated cell death mechanisms. Therapeutic hypothermia may improve functional outcome by attenuating trauma-induced oligodendrocyte cell death, subsequent demyelination and circuit dysfunction.

Damage to Myelin and Oligodendrocytes: A Role in Chronic Outcomes Following Traumatic Brain Injury?

“…Within the recent TAI literature, however, attention is beginning to be focused upon responses by central myelin and oligodendrocytes after TAI [9,10,11]. …”

Repeated Pediatric Concussions Evoke Long-Term Oligodendrocyte and White Matter Microstructural Dysregulation Distant from the Injury

“…Nonetheless, our results do indicate that pediatric mTBI not only dysregulates OL lineage cell formation but will ultimately lead to increased levels of mature OLs, especially when the injury is repeated. Adult TBI has been shown to lead to apoptosis of existing OLs followed by remyelination [78-80]. However, considering the incomplete myelination in AC at the time of TBI [81] and the fact that many OLs are undergoing development at this age [24-26], it is likely that the OL lineage cell development and maturation itself are altered, leading to abnormal WM development.…”

Hypothermia in Stroke Therapy: Systemic versus Local Application

“…However, another study in fetal sheep countered these results by showing that delayed cerebral hypothermia partially protects white mater after global cerebral ischemia by stimulating oligodendrocyte proliferation, reducing microglial induction, and restoring the amount and patern of expression of myelin basic protein, once again conirming the neuroprotective role of hypothermia toward oligodendrogenesis [129,130]. Moreover, researchers have found that hypothermia atenuates demyelination, trauma-induced oligodendrocyte cell death, and overall circuit dysfunction [131,132]. While a study in preterm fetal sheep found that TH was correlated with an overall reduction in the hypoxia-induced death of immature oligodendrocytes, hypothermia did not prevent the hypoxia-induced inhibition of oligodendrocyte proliferation in the periventricular white mater zone [133,134].…”

“…Since astrocytes are the largest population of cells present in the ischemic core during the subacute to chronic period of stroke, astrogliogenesis is often considered to be therapeutic following insult to the brain [131,135,136]. However, we still lack much information and need more investigation in this area.…”