Delayed melatonin administration promotes neuronal survival, neurogenesis and motor recovery, and attenuates hyperactivity and anxiety after mild focal cerebral ischemia in mice

Kılıç, Ertuğrul; Kılıç, Ülkan; Bacigaluppi, Marco; Guo, Zeyun; ́Abdallah, Nada Ben; Wolfer, David P; Reíter, Russel J.; Hermann, Dirk M.; Bassetti, Claudio L.

doi:10.1111/j.1600-079x.2008.00568.x

Cited by 121 publications

(109 citation statements)

References 47 publications

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“…However, circadian fluctuations are imme diately ablated, and not restored, in animals that sustain injury from global cerebral ischemia. In murine models of focal ischemia, hyperactivity has been described previously and its level has been associated with severity of brain injury [16,17]. The depth of spontaneous hypothermia induced by CA/CPR, even in the presence of persistent physical activity, is surprising.…”

Section: Discussionmentioning

confidence: 99%

Experimental Hyperthermia during Cardiac Arrest and CPR Is Associated with Severe Spontaneous Hypothermia in Mice

Noppens¹,

Kofler²,

Traystman³

2012

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Background: Since genetically engineered mice are becoming more and more available, these animals become of high interest to study physiologic and pathophysiologic pathways of brain ischemia. The aim of this study was to examine body temperature (Tb), physical activity variation and neurohistopathology in mice exposed to normothermic and hyperthermic cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Methods: Male C57Bl/6 mice weighing 22 -27 g were implanted intraperitoneally with a radio telemeter and subjected to 10 min cardiac arrest followed by cardiopulmonary resuscitation. Normothermia (37.5˚C) or hyperthermia (39.0˚C) was induced by controlling peri-cranial temperature during the arrest period. Results: Hyperthermia during the arrest resulted in a Tb decrease during early recovery to a nadir of 28˚C ± 0.8˚C (mean ± SE) and partially recovered to 34.4˚C ± 1˚C 36 hrs after CA/CPR. With normothermia during the arrest, Tb depression was less pronounced (nadir of 32.3˚C ± 0.3˚C) and recovered to physiologic levels within 24 hrs. Coupling of physical activity and body temperature was absent in all animals after CA/CPR. Neuronal injury in the caudoputamen was greater in the hyperthermia group. Conclusions: This study demonstrates that CA/CPR eliminates normal connectivity between body temperature and physical activity and induces long-lasting hypothermia, the depth of which is related to severity of brain injury. Long term temperature monitoring is required in survival murine experiments, if body temperature is a study variable.

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Section: Discussionmentioning

confidence: 99%

Experimental Hyperthermia during Cardiac Arrest and CPR Is Associated with Severe Spontaneous Hypothermia in Mice

Noppens¹,

Kofler²,

Traystman³

2012

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“…This effect, which is evidenced by reduced infarct volume, necrotic neuronal death, together with diminished neurologic deficits and increased number of surviving neurons, can shield brain function [90]. The beneficial properties of melatonin in countering stroke injury can be manifested even if administered 24 h after an ischemic lesion [91].…”

Section: The Potential For Melatonin Treatment Of Specific Neurologicmentioning

confidence: 99%

Melatonin, Oxidative Stress, and the Aging Brain

Bondy

Sharman

2010

Aging and Age-Related Disorders

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The changes associated with brain aging are discussed with emphasis on altered oxidative and inflammatory events and on mitochondrial dysfunction. Many of these changes are exacerbated in a variety of age-related neurologic diseases. This commonality has led to the idea that similar therapeutic approaches may be used in the treatment of several apparently unrelated neurodegenerative disorders. When aspects of these diseases are modeled in experimental animals and cell lines, the application of melatonin has been reported to be advantageous. The means by which melatonin can be protective probably is mediated by way of activation of melatonin receptors, of which several subtypes can be identified. This can initiate a sequence of intracellular signaling events and by activation of transcription factors lead to altered gene expression. The culmination of this cascade can lead to increased levels of antioxidant enzymes and depressed levels of inflammation. Melatonin may be useful both in the retardation of nonpathologic brain aging and in the amelioration of chronic brain disease associated with aging. The inexpensive nature and ready availability of melatonin together with its very low toxicity reinforce the need to place the beneficial properties of this agent on a firmer basis.

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“…4,5 It has previously been shown that the latency to move is prolonged up to several days after cerebral ischemia. 6 In our study, the latency to move one body length was, as expected, increased after the stroke in wild-type mice, but the time needed was significantly less in double-knockout than in wild-type mice 48 h after permanent distal MCAO (Fig.…”

Section: Latency-to-move Testmentioning

confidence: 99%