An analysis of regional microvascular loss and recovery following two grades of fluid percussion trauma: a role for hypoxia-inducible factors in traumatic brain injury.
Secondary hypoxic/ischemic injuries, stemming from reductions in cerebral blood flow are important contributing factors in progressive neuronal dysfunction after brain trauma. A greater preclinical understanding of how brain trauma leads to secondary hypoxia/ischemia is necessary in the development of posttraumatic brain injury (TBI) therapeutics. To this end, we examined the density of microvascular coverage in the injured and contralateral cortical hemispheres using two intensities of fluid percussion trauma in rats. A silicone microangiography technique showed a significant loss in microvascular density in 2 atmosphere (atm) (16.9+/-3.8%) and 3 atm (15.7+/-1.3%) injured animals relative to sham animals (29.9+/-2.5%; P<0.01). RECA-1 immunohistochemistry indicated that capillary changes involved a reduction in capillary number and diameter. Reduction in microvascular density was shown to be a diffuse phenomenon occurring up to 4 mm rostral and caudal to the injury epicenter. Recovery of microvasculature occurred by 2 weeks after injury only in the 2 atm injury group. Expression of HIF1alpha and increased vascular endothelial growth factor expression were observed in the ipsilateral hippocampus suggesting sufficiently impaired microcirculation resulting in the expression of hypoxic-response proteins. Collectively, the results indicate diffuse and heterogeneous microvascular alterations as well as endogenous expression of neuroprotective and neovascularization pathways after TBI.
Park
Eugene
E
Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Cara Phelan Centre for Trauma Research, Ontario, Canada. parke@smh.toronto.on.ca
Bell
Joshua D
JD
Siddiq
Ishita P
IP
Baker
Andrew J
AJ
D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002533:Cerebral Angiography; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation / Q000502:physiology / Q000528:radiation effects; D055806:Microvessels / Q000473:pathology*; D010474:Percussion; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism
C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat