Acute neuronal injury, excitotoxicity, and the endocannabinoid system

Mario Van der Stelt, Wouter B. Veldhuis, Mauro Maccarrone, Peter R. Bär, Klaas Nicolay, Gerrit A. Veldink, Vincenzo Di Marzo, Johannes F G Vliegenthart

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

The endocannabinoid system is a valuable target for drug discovery, because it is involved in the regulation of many cellular and physiological functions. The endocannabinoid system constitutes the endogenous lipids anandamide, 2-arachidonoylglycerol and noladin ether, and the cannabinoid CB1 and CB2 receptors as well as the proteins for their inactivation. It is thought that (endo)cannabinoid-based drugs may potentially be useful to reduce the effects of neurodegeneration. This paper reviews recent developments in the endocannabinoid system and its involvement in neuroprotection. Exogenous (endo)cannabinoids have been shown to exert neuroprotection in a variety of in vitro and in vivo models of neuronal injury via different mechanisms, such as prevention of excitotoxicity by CB1-mediated inhibition of glutamatergic transmission, reduction of calcium influx, and subsequent inhibition of deleterious cascades, TNF-α formation, and anti-oxidant activity. It has been suggested that the release of endogenous endocannabinoids during neuronal injury might be a protective response. However, several observations indicate that the role of the endocannabinoid system as a general endogenous protection system is questionable. The data are critically reviewed and possible explanations are given.

Original languageEnglish
Pages (from-to)317-346
Number of pages30
JournalMolecular Neurobiology
Volume26
Issue number2-3
DOIs
Publication statusPublished - Oct 2002

Fingerprint

Endocannabinoids
Wounds and Injuries
Cannabinoids
Cannabinoid Receptor CB2
Cannabinoid Receptor CB1
Drug Discovery
Oxidants
Calcium
Lipids
Pharmaceutical Preparations
Proteins

Keywords

  • 2-arachidonoylglycerol
  • Anandamide
  • Cannabinoid
  • Excitotoxicity
  • Neurodegeneration
  • Neuroprotection

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Cite this

Van der Stelt, M., Veldhuis, W. B., Maccarrone, M., Bär, P. R., Nicolay, K., Veldink, G. A., ... Vliegenthart, J. F. G. (2002). Acute neuronal injury, excitotoxicity, and the endocannabinoid system. Molecular Neurobiology, 26(2-3), 317-346. https://doi.org/10.1385/MN:26:2-3:317

Acute neuronal injury, excitotoxicity, and the endocannabinoid system. / Van der Stelt, Mario; Veldhuis, Wouter B.; Maccarrone, Mauro; Bär, Peter R.; Nicolay, Klaas; Veldink, Gerrit A.; Di Marzo, Vincenzo; Vliegenthart, Johannes F G.

In: Molecular Neurobiology, Vol. 26, No. 2-3, 10.2002, p. 317-346.

Research output: Contribution to journalArticle

Van der Stelt, M, Veldhuis, WB, Maccarrone, M, Bär, PR, Nicolay, K, Veldink, GA, Di Marzo, V & Vliegenthart, JFG 2002, 'Acute neuronal injury, excitotoxicity, and the endocannabinoid system', Molecular Neurobiology, vol. 26, no. 2-3, pp. 317-346. https://doi.org/10.1385/MN:26:2-3:317
Van der Stelt M, Veldhuis WB, Maccarrone M, Bär PR, Nicolay K, Veldink GA et al. Acute neuronal injury, excitotoxicity, and the endocannabinoid system. Molecular Neurobiology. 2002 Oct;26(2-3):317-346. https://doi.org/10.1385/MN:26:2-3:317
Van der Stelt, Mario ; Veldhuis, Wouter B. ; Maccarrone, Mauro ; Bär, Peter R. ; Nicolay, Klaas ; Veldink, Gerrit A. ; Di Marzo, Vincenzo ; Vliegenthart, Johannes F G. / Acute neuronal injury, excitotoxicity, and the endocannabinoid system. In: Molecular Neurobiology. 2002 ; Vol. 26, No. 2-3. pp. 317-346.
@article{a67f3c6fdf19452aa93510535c847fb3,
title = "Acute neuronal injury, excitotoxicity, and the endocannabinoid system",
abstract = "The endocannabinoid system is a valuable target for drug discovery, because it is involved in the regulation of many cellular and physiological functions. The endocannabinoid system constitutes the endogenous lipids anandamide, 2-arachidonoylglycerol and noladin ether, and the cannabinoid CB1 and CB2 receptors as well as the proteins for their inactivation. It is thought that (endo)cannabinoid-based drugs may potentially be useful to reduce the effects of neurodegeneration. This paper reviews recent developments in the endocannabinoid system and its involvement in neuroprotection. Exogenous (endo)cannabinoids have been shown to exert neuroprotection in a variety of in vitro and in vivo models of neuronal injury via different mechanisms, such as prevention of excitotoxicity by CB1-mediated inhibition of glutamatergic transmission, reduction of calcium influx, and subsequent inhibition of deleterious cascades, TNF-α formation, and anti-oxidant activity. It has been suggested that the release of endogenous endocannabinoids during neuronal injury might be a protective response. However, several observations indicate that the role of the endocannabinoid system as a general endogenous protection system is questionable. The data are critically reviewed and possible explanations are given.",
keywords = "2-arachidonoylglycerol, Anandamide, Cannabinoid, Excitotoxicity, Neurodegeneration, Neuroprotection",
author = "{Van der Stelt}, Mario and Veldhuis, {Wouter B.} and Mauro Maccarrone and B{\"a}r, {Peter R.} and Klaas Nicolay and Veldink, {Gerrit A.} and {Di Marzo}, Vincenzo and Vliegenthart, {Johannes F G}",
year = "2002",
month = "10",
doi = "10.1385/MN:26:2-3:317",
language = "English",
volume = "26",
pages = "317--346",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Humana Press Inc.",
number = "2-3",

}

TY - JOUR

T1 - Acute neuronal injury, excitotoxicity, and the endocannabinoid system

AU - Van der Stelt, Mario

AU - Veldhuis, Wouter B.

AU - Maccarrone, Mauro

AU - Bär, Peter R.

AU - Nicolay, Klaas

AU - Veldink, Gerrit A.

AU - Di Marzo, Vincenzo

AU - Vliegenthart, Johannes F G

PY - 2002/10

Y1 - 2002/10

N2 - The endocannabinoid system is a valuable target for drug discovery, because it is involved in the regulation of many cellular and physiological functions. The endocannabinoid system constitutes the endogenous lipids anandamide, 2-arachidonoylglycerol and noladin ether, and the cannabinoid CB1 and CB2 receptors as well as the proteins for their inactivation. It is thought that (endo)cannabinoid-based drugs may potentially be useful to reduce the effects of neurodegeneration. This paper reviews recent developments in the endocannabinoid system and its involvement in neuroprotection. Exogenous (endo)cannabinoids have been shown to exert neuroprotection in a variety of in vitro and in vivo models of neuronal injury via different mechanisms, such as prevention of excitotoxicity by CB1-mediated inhibition of glutamatergic transmission, reduction of calcium influx, and subsequent inhibition of deleterious cascades, TNF-α formation, and anti-oxidant activity. It has been suggested that the release of endogenous endocannabinoids during neuronal injury might be a protective response. However, several observations indicate that the role of the endocannabinoid system as a general endogenous protection system is questionable. The data are critically reviewed and possible explanations are given.

AB - The endocannabinoid system is a valuable target for drug discovery, because it is involved in the regulation of many cellular and physiological functions. The endocannabinoid system constitutes the endogenous lipids anandamide, 2-arachidonoylglycerol and noladin ether, and the cannabinoid CB1 and CB2 receptors as well as the proteins for their inactivation. It is thought that (endo)cannabinoid-based drugs may potentially be useful to reduce the effects of neurodegeneration. This paper reviews recent developments in the endocannabinoid system and its involvement in neuroprotection. Exogenous (endo)cannabinoids have been shown to exert neuroprotection in a variety of in vitro and in vivo models of neuronal injury via different mechanisms, such as prevention of excitotoxicity by CB1-mediated inhibition of glutamatergic transmission, reduction of calcium influx, and subsequent inhibition of deleterious cascades, TNF-α formation, and anti-oxidant activity. It has been suggested that the release of endogenous endocannabinoids during neuronal injury might be a protective response. However, several observations indicate that the role of the endocannabinoid system as a general endogenous protection system is questionable. The data are critically reviewed and possible explanations are given.

KW - 2-arachidonoylglycerol

KW - Anandamide

KW - Cannabinoid

KW - Excitotoxicity

KW - Neurodegeneration

KW - Neuroprotection

UR - http://www.scopus.com/inward/record.url?scp=0036773310&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036773310&partnerID=8YFLogxK

U2 - 10.1385/MN:26:2-3:317

DO - 10.1385/MN:26:2-3:317

M3 - Article

VL - 26

SP - 317

EP - 346

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

IS - 2-3

ER -