Changes in local microvascular permeability and in the effect of intervention with 21-aminosteroid (Tirilazad) in a new experimental model of focal cortical injury in the rat.
In a new, reproducible model of rodent focal cortical injury, we have shown that in the absence of early traumatic disruption of the microvasculature and subsequent hemorrhage, delayed perivascular protein leakage and polymorphonuclear leukocyte infiltration of the injured cortex occur. In this study we employed a sensitive quantitative autoradiographic technique (using alpha-aminoisobutyric acid as a tracer) to investigate the focal changes in microvascular permeability with time and to determine the effects of administration of a 21-aminosteroid (Tirilazad) initiated 5 min after induction of the cortical injury. At all time points studied, there was a significant increase in perilesional blood-brain barrier permeability in lesioned animals treated with vehicle, compared to shamoperated animals, with the most marked increase in blood-brain barrier permeability at 4 h postinjury (mean Ki +/- SE = 19.2 +/- 2.4/1000 min with cortical injury, 1.5 +/- 0.3/1000 min in shams) (mean volume +/- SE = 15.48 +/- 0.7 mm3). In animals with cortical injury treated with Tirilazad (10 mg/kg), there was a significant reduction in microvascular permeability at the site of injury (Ki = 3.1 +/- 0.5, p < 0.001) and a significant reduction in volume of increased permeability (4.86 +/- 0.7 mm3, p < 0.01) at 4 h postinjury. In this model of cortical injury, a delayed increase in microvascular permeability occurs, which is significantly attenuated by postinjury treatment with Tirilazad.
Mathew
P
P
Department of Neurosurgery, Southern General Hospital, Glasgow, Scotland.
Bullock
R
R
Teasdale
G
G
McCulloch
J
J
D000704:Analysis of Variance; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001930:Brain Injuries / Q000503:physiopathology*; D002199:Capillary Permeability / Q000187:drug effects; D002540:Cerebral Cortex / Q000098:blood supply* / Q000187:drug effects / Q000293:injuries; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D008833:Microcirculation / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018696:Neuroprotective Agents; D011281:Pregnatrienes; C053355:tirilazad