Long-term morphological and functional evaluation of the neuroprotective effects of post-ischemic treatment with melatonin in rats.
Consensus on neuroprotection has pointed out the relevance of the long-term morphological and functional evaluation of the effectiveness of putative neuroprotective procedures. In the present study, place learning (Morris water maze) and working memory (eight-arm Olton radial maze) were evaluated in adult male rats 90 days after 15 min of global cerebral ischemia (four-vessel occlusion) followed by continuous i.v. infusion (10 mg/kg/hr) of melatonin (Isch + Mel) or vehicle (Isch + Veh) for 6 hr, and the pyramidal neuron population of the cornus Ammoni (CA) of the hippocampus and layers III and V of the medial prefrontal cortex was assessed at the end of the behavioral testing period (120 days after ischemia). Impairment of place learning, a significant delay in working memory acquisition, and a significant loss of pyramidal neurons in the Ammon's horn (CA1: 23%, CA2: 52% CA3: 73%, hilus: 64% remaining neurons), were observed in the Isch + Veh group. By contrast, a similar performance of the Isch + Mel group to that in the Intact and Sham groups and better than that of the Isch + Veh group, besides a significant reduction of pyramidal neuron loss in the CA subfields (CA1: 79%, CA2: 88% CA3: 86%, hilus: 72% remaining neurons), documented that melatonin treatment led to a long-term preservation of both the neural substrate, and the capability for integration of spatial learning and memory, mainly dependent on a normal hippocampal functioning. Overall the results emphasize the efficacy of melatonin in counteracting the pathophysiological processes induced by ischemia, by exerting its actions during a short but critical period early after the ischemic episode.
Letechipía-Vallejo
Graciela
G
Facultad de Ciencias Médicas y Biológicas Dr. Ignacio Chávez, UMSNH, Morelia, Michoacán, Spain.
López-Loeza
Elisa
E
Espinoza-González
Verónica
V
González-Burgos
Ignacio
I
Olvera-Cortés
María Esther
ME
Moralí
Gabriela
G
Cervantes
Miguel
M
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats
D018696:Neuroprotective Agents; D008550:Melatonin