Azelastine protects against CA1 traumatic neuronal injury in the hippocampal slice.
Activation of NMDA receptors appears to play a important role in traumatic neuronal injury. Additionally, N-methyl-D-aspartate (NMDA) excitotoxicity may involve leukotriene production. Therefore, we investigated whether azelastine, an anti-allergic agent inhibiting the synthesis and release of leukotrienes, could protect against CA1 traumatic neuronal injury in the hippocampal slice. Fluid percussion trauma produced evidence of severe neuronal injury with CA1 antidromic population spike amplitude recovering after 95 min to only a mean 16 +/- 1 % S.E. of initial amplitude. With 15 microM azelastine treatment given after trauma for 35 min this recovery improved to 112 +/- 17%. The azelastine EC50 for this protection was 10 microM. Significant protection was also seen with azelastine application begun 15 min after trauma. Azelastine also protected the ability to induce long-term potentiation after trauma. The specific leukotriene inhibitors, MK-571 and MK-886, similarly provided significant neuroprotection. These findings suggest that CA1 traumatic neuronal injury may be mediated by leukotriene production.
Girard
J
J
Neuronal Injury Laboratory (111N-1), Sepulveda VAMC, CA 91343, USA.
Panizzon
K
K
Wallis
R A
RA
D000818:Animals; D001930:Brain Injuries / Q000517:prevention & control*; D001993:Bronchodilator Agents / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials; D006624:Hippocampus / Q000187:drug effects / Q000293:injuries; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects*; D010793:Phthalazines / Q000627:therapeutic use*; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001993:Bronchodilator Agents; D006634:Histamine H1 Antagonists; D010793:Phthalazines; D011422:Propionates; D011804:Quinolines; C059141:verlukast; C020976:azelastine