Neuroprotective effects of hyperbaric oxygen treatment in experimental focal cerebral ischemia are associated with reduced brain leukocyte myeloperoxidase activity.
OBJECTIVE
Hyperbaric oxygen (HBO) reduces cerebral infarct size after middle cerebral artery occlusion (MCAO) in rats through an unknown mechanism. In other forms of injury, cellular protection with HBO is associated with diminished infiltration of polymorphonuclear neutrophils (PMN). We hypothesized that HBO given prior to or after MCAO reduces PMN infiltration into the brain, and that decreased PMN infiltration is associated with improved functional and anatomic outcome.


METHODS
Forty rats underwent MCAO and were randomized to pretreatment with HBO (3 ATA) immediately prior to (n=13), or posttreatment immediately after surgery (n=12), or to control (air 1 ATA) (n=15). Five rats underwent sham surgery. Neurologic outcome was measured at 24 h in all animals. Brain myeloperoxidase (MPO) activity (n=22) and infarct volume (n=23) were determined.


RESULTS
MPO activity was significantly higher in controls (mean 0.28, 95% C.I. 0.17-0.38) than in the HBO pretreatment group (0.12, 0.08-0.16), HBO posttreatment group (0.16, 0.13-0.19), and the sham group (0.02, -0.02 to 0.05). HBO treated animals also had better neurologic outcomes (pretreatment 1.5, 0.9-2.1, posttreatment 2.6, 2.0-3.2) and smaller infarcts (pretreatment 27%, 18-37%, posttreatment 28%, 19-37%) than controls (neurologic outcome 3.7, 3.1-4.4, infarct volume 39%, 30-48%). Neurologic outcomes correlate better with MPO activity (R(2)=0.75) than with infarct volume (R(2)=0.25).


CONCLUSIONS
These data confirm the neuroprotective effects of HBO in cerebral ischemia and suggest that the mechanism of this action may involve inhibition of PMN infiltration in the injured brain.
Miljkovic-Lolic
Milena
M
Department of Medicine, St Joseph Medical Center, Towson, MD, USA.
Silbergleit
Robert
R
Fiskum
Gary
G
Rosenthal
Robert E
RE
D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D006931:Hyperbaric Oxygenation; D020244:Infarction, Middle Cerebral Artery / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control* / Q000628:therapy*; D008297:Male; D009043:Motor Activity; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009504:Neutrophils / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D009195:Peroxidase