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

Ertugrul Kilic, Ülkan Kilic, Marco Bacigaluppi, Zeyun Guo, Nada Ben Abdallah, David P. Wolfer, Russel J. Reiter, Dirk M. Hermann, Claudio L. Bassetti

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Melatonin is a potent antioxidant with neuroprotective activity in animal models of ischemic stroke, which based on its lack of serious toxicity has raised hopes that it might be used for human stroke treatment in the future. This study investigated how subacute delivery of melatonin, starting at 24 hr after stroke onset, and continuing for 29 days (4 mg/kg/day; via drinking water), influences neuronal survival, endogenous neurogenesis, motor recovery and locomotor activity in C57Bl6/j mice submitted to 30-min middle cerebral artery occlusion. Histologic studies showed that melatonin improved neuronal survival and enhanced neurogenesis, even when applied 1 day after stroke. Cell survival was associated with a long-lasting improvement of motor and coordination deficits, evaluated by the grip strength and RotaRod tests, as well as with attenuation of hyperactivity and anxiety of the animals as revealed in open field tests. The robust functional neurologic improvements encourage proof-of-concept studies with melatonin in human stroke patients.

Original languageEnglish
Pages (from-to)142-148
Number of pages7
JournalJournal of Pineal Research
Volume45
Issue number2
DOIs
Publication statusPublished - Sep 2008

Fingerprint

Neurogenesis
Melatonin
Brain Ischemia
Anxiety
Stroke
Hope
Rotarod Performance Test
Middle Cerebral Artery Infarction
Hand Strength
Locomotion
Drinking Water
Nervous System
Cell Survival
Motor Activity
Animal Models
Antioxidants

Keywords

  • Anxiety
  • Free radical scavenger
  • Ischemic stroke
  • Locomotor activity
  • Motor coordination

ASJC Scopus subject areas

  • Endocrinology

Cite this

Delayed melatonin administration promotes neuronal survival, neurogenesis and motor recovery, and attenuates hyperactivity and anxiety after mild focal cerebral ischemia in mice. / Kilic, Ertugrul; Kilic, Ülkan; Bacigaluppi, Marco; Guo, Zeyun; Abdallah, Nada Ben; Wolfer, David P.; Reiter, Russel J.; Hermann, Dirk M.; Bassetti, Claudio L.

In: Journal of Pineal Research, Vol. 45, No. 2, 09.2008, p. 142-148.

Research output: Contribution to journalArticle

Kilic, Ertugrul ; Kilic, Ülkan ; Bacigaluppi, Marco ; Guo, Zeyun ; Abdallah, Nada Ben ; Wolfer, David P. ; Reiter, Russel J. ; Hermann, Dirk M. ; Bassetti, Claudio L. / Delayed melatonin administration promotes neuronal survival, neurogenesis and motor recovery, and attenuates hyperactivity and anxiety after mild focal cerebral ischemia in mice. In: Journal of Pineal Research. 2008 ; Vol. 45, No. 2. pp. 142-148.
@article{1265c1b765134d25ae50a7be171e84c1,
title = "Delayed melatonin administration promotes neuronal survival, neurogenesis and motor recovery, and attenuates hyperactivity and anxiety after mild focal cerebral ischemia in mice",
abstract = "Melatonin is a potent antioxidant with neuroprotective activity in animal models of ischemic stroke, which based on its lack of serious toxicity has raised hopes that it might be used for human stroke treatment in the future. This study investigated how subacute delivery of melatonin, starting at 24 hr after stroke onset, and continuing for 29 days (4 mg/kg/day; via drinking water), influences neuronal survival, endogenous neurogenesis, motor recovery and locomotor activity in C57Bl6/j mice submitted to 30-min middle cerebral artery occlusion. Histologic studies showed that melatonin improved neuronal survival and enhanced neurogenesis, even when applied 1 day after stroke. Cell survival was associated with a long-lasting improvement of motor and coordination deficits, evaluated by the grip strength and RotaRod tests, as well as with attenuation of hyperactivity and anxiety of the animals as revealed in open field tests. The robust functional neurologic improvements encourage proof-of-concept studies with melatonin in human stroke patients.",
keywords = "Anxiety, Free radical scavenger, Ischemic stroke, Locomotor activity, Motor coordination",
author = "Ertugrul Kilic and {\"U}lkan Kilic and Marco Bacigaluppi and Zeyun Guo and Abdallah, {Nada Ben} and Wolfer, {David P.} and Reiter, {Russel J.} and Hermann, {Dirk M.} and Bassetti, {Claudio L.}",
year = "2008",
month = "9",
doi = "10.1111/j.1600-079X.2008.00568.x",
language = "English",
volume = "45",
pages = "142--148",
journal = "Journal of Pineal Research",
issn = "0742-3098",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Delayed melatonin administration promotes neuronal survival, neurogenesis and motor recovery, and attenuates hyperactivity and anxiety after mild focal cerebral ischemia in mice

AU - Kilic, Ertugrul

AU - Kilic, Ülkan

AU - Bacigaluppi, Marco

AU - Guo, Zeyun

AU - Abdallah, Nada Ben

AU - Wolfer, David P.

AU - Reiter, Russel J.

AU - Hermann, Dirk M.

AU - Bassetti, Claudio L.

PY - 2008/9

Y1 - 2008/9

N2 - Melatonin is a potent antioxidant with neuroprotective activity in animal models of ischemic stroke, which based on its lack of serious toxicity has raised hopes that it might be used for human stroke treatment in the future. This study investigated how subacute delivery of melatonin, starting at 24 hr after stroke onset, and continuing for 29 days (4 mg/kg/day; via drinking water), influences neuronal survival, endogenous neurogenesis, motor recovery and locomotor activity in C57Bl6/j mice submitted to 30-min middle cerebral artery occlusion. Histologic studies showed that melatonin improved neuronal survival and enhanced neurogenesis, even when applied 1 day after stroke. Cell survival was associated with a long-lasting improvement of motor and coordination deficits, evaluated by the grip strength and RotaRod tests, as well as with attenuation of hyperactivity and anxiety of the animals as revealed in open field tests. The robust functional neurologic improvements encourage proof-of-concept studies with melatonin in human stroke patients.

AB - Melatonin is a potent antioxidant with neuroprotective activity in animal models of ischemic stroke, which based on its lack of serious toxicity has raised hopes that it might be used for human stroke treatment in the future. This study investigated how subacute delivery of melatonin, starting at 24 hr after stroke onset, and continuing for 29 days (4 mg/kg/day; via drinking water), influences neuronal survival, endogenous neurogenesis, motor recovery and locomotor activity in C57Bl6/j mice submitted to 30-min middle cerebral artery occlusion. Histologic studies showed that melatonin improved neuronal survival and enhanced neurogenesis, even when applied 1 day after stroke. Cell survival was associated with a long-lasting improvement of motor and coordination deficits, evaluated by the grip strength and RotaRod tests, as well as with attenuation of hyperactivity and anxiety of the animals as revealed in open field tests. The robust functional neurologic improvements encourage proof-of-concept studies with melatonin in human stroke patients.

KW - Anxiety

KW - Free radical scavenger

KW - Ischemic stroke

KW - Locomotor activity

KW - Motor coordination

UR - http://www.scopus.com/inward/record.url?scp=47349084792&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=47349084792&partnerID=8YFLogxK

U2 - 10.1111/j.1600-079X.2008.00568.x

DO - 10.1111/j.1600-079X.2008.00568.x

M3 - Article

VL - 45

SP - 142

EP - 148

JO - Journal of Pineal Research

JF - Journal of Pineal Research

SN - 0742-3098

IS - 2

ER -