p-Chlorophenylalanine, an inhibitor of serotonin synthesis reduces blood-brain barrier permeability, cerebral blood flow, edema formation and cell injury following trauma to the rat brain.
The role of serotonin in trauma induced alterations in blood-brain barrier (BBB) permeability, cerebral blood flow (CBF), brain edema and cell changes were examined in a new model of cortical injury in the rat using a pharmacological approach. A longitudinal incision into the right parietal cerebral cortex (about 3 mm deep and 5 mm long) was associated with a profound increase in the BBB permeability to Evans blue and [131]I-sodium, brain water content, and a reduction in the CBF in both the ipsilateral and contralateral hemispheres 5 h after trauma. Nissl staining showed a profound nerve cell reaction in the parietal cerebral cortex of both hemispheres. The intensity of these pathological changes was most pronounced in the traumatised hemisphere. Pretreatment with p-CPA, a serotonin synthesis inhibitor, significantly attenuated breakdown of the BBB permeability, brain edema and the CBF disturbances. Damaged and distorted nerve cells were markedly less frequent in p-CPA treated rats. This effect of the drug was most pronounced in the contralateral hemisphere. The observations strongly suggest that serotonin is one of the important neurochemical mediators of BBB permeability disturbances and brain edema formation in the trauma induced brain damage.
Sharma
H S
HS
Laboratory of Neuroanatomy, Department of Medical Cell Biology, Biomedical Centre, Uppsala University, Uppsala, Sweden.
Winkler
T
T
Stålberg
E
E
Mohanty
S
S
Westman
J
J
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000098:blood supply*; D001929:Brain Edema / Q000473:pathology*; D001930:Brain Injuries / Q000473:pathology*; D002199:Capillary Permeability / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D004292:Dominance, Cerebral / Q000187:drug effects; D010134:Fenclonine / Q000494:pharmacology*; D010296:Parietal Lobe / Q000293:injuries* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology*
D012702:Serotonin Antagonists; D012701:Serotonin; D010134:Fenclonine