title: Neuroprotective effects of nimodipine and MK-801 on acute infectious brain edema induced by injection of pertussis bacilli to neocortex of rats.
abstract: OBJECTIVE
  To explore the mechanism and type of acute infectious brain edema induced by injection of pertussis bacilli (PB) in rat neocortex, to study the neuroprotective effect of non-competitive antagonist of N-methl-D-aspartate (NMDA) receptor (MK-801) and antagonist of Ca(2+) channels (nimodipine) on brain edema, and to investigate the relationship between percentage of water content and cytosolic free calcium concentration ([Ca(2+) ](i)) in synaptosomes or content of Evans Blue (EB).
  
  
  METHODS
  95 SD rats were randomly divided into five groups, ie, normal control group, sham-operated control group, PB group, nimodipine treatment group and MK-801 pretreatment group. The acute infectious brain edema was induced by injection of PB into the rats. Quantitative measurements of water content and the concentration of EB were performed. [Ca(2+) ](i) was determined in calcium fluorescent indication Fura-2/AM loaded neuronal synaptosome with a spectrofluorophotometer. To observe the effect of MK-801 and nimodipine, we administered MK-801 48 hours and 24 hours before the injection of PB in MK-801 pretreatment group, and nimodipine after the injection of PB in nimodipine treatment group. The specific binding of NMDA receptor was measured with [(3)H]-MK-801 in the neuronal membrane of cerebral cortex.
  
  
  RESULTS
  The levels of water content and EB content of brain tissues, and [Ca(2+) ](i) in the neuronal synaptosomes increased more significantly in the PB-injected cerebral hemisphere in the PB group than those of normal control group and sham-operated control group (P<0.05). The water content and [Ca(2+) ](i) increased with the duration of infectious brain edema. Nimodipine administered after the injection of PB could significantly decrease the water content, EB and [Ca(2+) ](i) (P<0.05). MK-801 could significantly decrease the water content, EB and [Ca(2+) ](i) in 4 h and 24 h groups (P<0.05). The Kd values were 30.5 nmol/L+/-3.0 nmol/L and 42.1 nmol/L+/-4.2 nmol/L in PB group and NS group respectively (P<0.05), and Bmax were 0.606 pmol/mg.pro+/-0.087 pmol/mg.pro and 0.623 pmol/mg.pro+/-0.082 pmol/mg.pro respectively, without statistical significance (P>0.05).
  
  
  CONCLUSIONS
  The changes in the permeability of blood-brain barrier (BBB) and Ca(2+)-overload may participate in the pathogenesis of infectious brain edema. Treatment with nimodipine can dramatically reduce the damage of brain edema and demonstrate neuroprotective effect on brain edema by inhibiting the excess of Ca(2+) influx and reducing the permeability of BBB. MK-801 pretreatment may inhibit the delayed Ca(2+) influx into the neurons. The infectious brain edema is not only cytotoxic brain edema (intracellular edema) but also vasogenic brain edema (extracellular edema) followed by earlier BBB breakdown, so infectious brain edema is complicated with brain edema.
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China. chenlihua-llx@163.net
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Chen
authors.forename: Li-Xu
authors.initials: LX
authors.lastname: Liu
authors.forename: Yu-Jia
authors.initials: YJ
authors.lastname: Yang
authors.forename: Yun-Sheng
authors.initials: YS
authors.lastname: Liu
authors.forename: Mei-Hong
authors.initials: MH
authors.lastname: Cao
mesh_terms: D000208:Acute Disease; D000704:Analysis of Variance; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001886:Bordetella pertussis; D001929:Brain Edema / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002121:Calcium Channel Blockers; D009553:Nimodipine; D016291:Dizocilpine Maleate; D002118:Calcium