Methylprednisolone treatment delays remote cell death after focal brain lesion.
Glucocorticoids have a prominent role in the treatment of CNS injuries. However, the cellular consequences of glucocorticoid treatment on remote degenerative responses after focal brain lesions have been poorly investigated. Here we examine the effectiveness of a high dose (50 mg/kg) of methylprednisolone sodium succinate (MPSS) in reducing neuronal loss, glial response and glial-derived inflammatory mediators in inferior olive and pontine nuclei after lesion of the contralateral cerebellar hemisphere using immunohistochemistry and Western blot techniques. Quantitative analysis demonstrated that MPSS treatment significantly improved the survival of neurons in remote precerebellar stations. This survival was accompanied by reduction in the postlesional activation of microglia, astrocytes and interleukin-1 beta (IL-1beta). Cell death resumed after suspension of MPSS treatment and this delayed wave of cell loss was paralleled by reactivation of the inflammatory markers analyzed. The present study confirms the importance of inflammatory events in inducing remote cell death and that this type of degeneration can be delayed by MPSS treatment. Furthermore, the sustained effect of MPSS treatment, up to 28 days postlesion, and the reactivation of the degenerative phenomena after its suspension, support the hypothesis that glucocorticoid treatment, although capable of delaying cell death mechanisms, is not effective in blocking the cascade of remote degenerative events started by the primary lesion.
Santa Lucia Foundation Istituto Ricovero e Cura Carattere Scientifico, Rome, Italy.
M T
MT
Viscomi
F
F
Florenzano
L
L
Latini
D
D
Amantea
G
G
Bernardi
M
M
Molinari
D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects* / Q000293:injuries*; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D018613:Microscopy, Confocal; D009410:Nerve Degeneration / Q000473:pathology / Q000517:prevention & control*; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018696:Neuroprotective Agents; D008775:Methylprednisolone