Nitric oxide in the pathophysiology of hyperthermic brain injury. Influence of a new anti-oxidant compound H-290/51. A pharmacological study using immunohistochemistry in the rat.
The possibility that nitric oxide (NO) is involved in the pathophysiology of brain injury caused by heat stress (HS) was examined using neuronal nitric oxide synthase (NOS) immunohistochemistry in a rat model. In addition, to find out a role of oxidative stress in NOS upregulation and cell injury, the effect of a new antioxidant compound H-290/51 (Astra Hässle, Mölndal, 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 degree C). This NOS immunoreactivity was found mainly in distorted neurons located in the edematous regions not normally showing NOS 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 upregulation of NOS activity. Pretreatment with H-290/51 significantly attenuated the upregulation of NOS in rats subjected to HS. In these animals breakdown of the BBB permeability, edema and cell changes were considerably reduced. Our results suggest that hyperthermic brain injury is associated with a marked upregulation of NOS activity in the CNS and this upregulation of NOS and concomitant cell injury can be reduced by prior treatment with an antioxidant compound H 290/51. These observations indicate that oxidative stress seems to be an important endogenous signals for NOS upregulation and cell reaction in hyperthermic brain injury.
Alm
P
P
Department of Pathology, University Hospital, University of Lund, Sweden.
Sharma
H S
HS
Hedlund
S
S
Sjöquist
P O
PO
Westman
J
J
D000818:Animals; D001929:Brain Edema / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology; D001930:Brain Injuries / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology*; D002199:Capillary Permeability; D005334:Fever / Q000150:complications / Q000201:enzymology / Q000503:physiopathology*; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
C088233:H290-51; D007211:Indoles; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase