Method of treating or inhibiting the development of brain inflammation and sepsis

Abstract

A leukotriene C4 and D4 antagonist is used to treat or inhibit brain inflammation and sepsis by acting to inhibit increased capillary permeability and white blood cell extravasation. Potential candidate compounds can be screened in a non-human mammal before or after administration of an inflammation inducing agent into the subarachnoid space by determining their ability to inhibit increased capillary permeability and white blood cell extravasation.

1 . A method for screening an inhibitor of increased capillary permeability, comprising: 
 administering a potential candidate inhibitor compound to a non-human mammal before or after an inflammation-inducing agent is introduced into the subarachnoid space via a cannula inserted therein through the dura mater of the brain of the non-human mammal;    measuring the amount of cerebrospinal fluid collected through the cannula; and    determining from the measured amount of collected cerebrospinal fluid if the potential candidate inhibitor compound is an inhibitor of increased capillary permeability.    
   
   
       2 . The method of  claim 1 , wherein the inflammation-inducing agent is selected from the group consisting of arachidonic acid, prostaglandin, thromboxane, histamine, LPS, dextran, bradykinin, carrageenan, leukotriene, TNFα, IL-1β, and IL-6.  
   
   
       3 . The method of  claim 1 , further comprising measuring the white blood cell count in the cerebrospinal fluid collected.