NITRIC-OXIDE IN THE PATHOPHYSIOLOGY OF HYPERTHERMIC BRAIN INJURY - INFLUENCE OF A NEW ANTIOXIDANT COMPOUND H-290 51 - A PHARMACOLOGICAL STUDY USING IMMUNOHISTOCHEMISTRY IN THE RAT/

The possibility that nitric oxide (NO) is involved in the pathophysiol ogy of brain injury caused by heat stress (HS) was examined using neur onal nitric oxide synthase (NOS) immunohistochemistry in a rat model. In addition, to find out a role of oxidative stress in NOS upregulatio n and cell injury, the effect of a new antioxidant compound H-290/51 ( Astra Hassle. Molndal, Sweden) was examined in this model. Subjection of conscious young rats to 4 h HS in a biological oxygen demand (BOD) incubator at 38 degrees C resulted in a marked upregulation of NOS in many brain regions compared to control rats kept at room temperature ( 21 +/- 1 degrees C). This NOS immunoreactivity was found mainly in dis torted neurons located in the edematous regions not normally showing N OS activity. Breakdown of the blood-brain barrier (BBB) permeability, increase in brain water content and marked neuronal, glial and myelin reaction were common findings in several brain regions exhibiting upre gulation of NOS activity. Pretreatment with H-290/51 significantly att enuated the upregulation of NOS in rats subjected to HS. In these anim als breakdown of the BBB permeability, edema and cell changes were con siderably reduced. Our results suggest that hyperthermic brain injury is associated with a marked upregulation of NOS activity in the CNS an d this upregulation of NOS and concomitant cell injury can be reduced by prior treatment with an antioxidant compound H 290/51. These observ ations indicate that oxidative stress seems to be an important endogen ous signals for NOS upregulation and cell reaction in hyperthermic bra in injury.