Neurotoxicity, blood-brain barrier breakdown, demyelination and remyelination associated with NMDA-induced lesions of the rat lateral hypothalamus

Helen Brace, Mary Latimer, Philip Winn

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Excitotoxins have been widely used to make lesions in the brains of experimental animals because they have the ability to destroy neurones while sparing fibres of passage. Because loss of fibres of passage can confound the interpretation of lesion effects, this property is of considerable value. Recently, however, there have been reports indicating that excitotoxins acting at different sites within the rat CNS not only destroy neurones but also strip myelin from fibres and compromise the integrity of the blood- brain barrier. However, some reports also indicate that the myelin content of the lesioned area recovers. Excitotoxic lesions of the lateral hypothalamus have been shown to produce local demyelination. The present studies sought to investigate this effect further by (1) defining the time course of demyelination and possible remyelination after excitotoxic lesions of the lateral hypothalamus made with N-methyl-D-aspartate (NMDA); (2) establishing the relationships between neuronal loss, de- and remyelination after various doses of NMDA; and (3) examining the integrity of the blood-brain barrier using an immunohistochemical probe. Our data show that after injection of NMDA into the lateral hypothalamus there was neuronal loss, blood-brain barrier disruption (followed by recovery over approximately 12 days), triggering of reactive gliosis, invasion of the lesioned area by cells from outwith the CNS, demyelination over an area coexistent with but not exceeding the area of neuronal loss, and remyelination. Remyelination occurred over a period of 3 months following the production of the lesion and was associated initially with blood vessels. It occurred across the whole of the lesioned area, not by encroachment from the borders. All doses of NMDA that produced neuronal death also produced demyelination. These data confirm that excitotoxic lesions of the lateral hypothalamus demyelinate fibres, but show for the first time that remyelination occurs here. They are consistent with reports concerning excitotoxin actions at other CNS sites and indicate that de- and remyelination after excitotoxic lesions is a ubiquitous process. Consideration should be given to this when using excitotoxins to make fibre- sparing lesions.

Original languageEnglish
Pages (from-to)447-455
Number of pages9
JournalBrain Research Bulletin
Volume43
Issue number5
DOIs
Publication statusPublished - 1 Jun 1997

Fingerprint

Lateral Hypothalamic Area
Demyelinating Diseases
N-Methylaspartate
Blood-Brain Barrier
Neurotoxins
Myelin Sheath
Neurons
Gliosis
Blood Vessels
Injections
Brain

Keywords

  • blood-brain barrier
  • demyelination
  • excitotoxin
  • lateral hypothalamus
  • N- methyl-D-aspartate
  • remyelination
  • neurotoxicity
  • n methyl dextro aspartic acid
  • animal tissue
  • hypothalamus nucleus
  • pathophysiology
  • myelin sheath

Cite this

@article{72192e0ac832473cb698f69a55036f2e,
title = "Neurotoxicity, blood-brain barrier breakdown, demyelination and remyelination associated with NMDA-induced lesions of the rat lateral hypothalamus",
abstract = "Excitotoxins have been widely used to make lesions in the brains of experimental animals because they have the ability to destroy neurones while sparing fibres of passage. Because loss of fibres of passage can confound the interpretation of lesion effects, this property is of considerable value. Recently, however, there have been reports indicating that excitotoxins acting at different sites within the rat CNS not only destroy neurones but also strip myelin from fibres and compromise the integrity of the blood- brain barrier. However, some reports also indicate that the myelin content of the lesioned area recovers. Excitotoxic lesions of the lateral hypothalamus have been shown to produce local demyelination. The present studies sought to investigate this effect further by (1) defining the time course of demyelination and possible remyelination after excitotoxic lesions of the lateral hypothalamus made with N-methyl-D-aspartate (NMDA); (2) establishing the relationships between neuronal loss, de- and remyelination after various doses of NMDA; and (3) examining the integrity of the blood-brain barrier using an immunohistochemical probe. Our data show that after injection of NMDA into the lateral hypothalamus there was neuronal loss, blood-brain barrier disruption (followed by recovery over approximately 12 days), triggering of reactive gliosis, invasion of the lesioned area by cells from outwith the CNS, demyelination over an area coexistent with but not exceeding the area of neuronal loss, and remyelination. Remyelination occurred over a period of 3 months following the production of the lesion and was associated initially with blood vessels. It occurred across the whole of the lesioned area, not by encroachment from the borders. All doses of NMDA that produced neuronal death also produced demyelination. These data confirm that excitotoxic lesions of the lateral hypothalamus demyelinate fibres, but show for the first time that remyelination occurs here. They are consistent with reports concerning excitotoxin actions at other CNS sites and indicate that de- and remyelination after excitotoxic lesions is a ubiquitous process. Consideration should be given to this when using excitotoxins to make fibre- sparing lesions.",
keywords = "blood-brain barrier, demyelination, excitotoxin, lateral hypothalamus, N- methyl-D-aspartate, remyelination, neurotoxicity, n methyl dextro aspartic acid, animal tissue, hypothalamus nucleus, pathophysiology, myelin sheath",
author = "Helen Brace and Mary Latimer and Philip Winn",
year = "1997",
month = "6",
day = "1",
doi = "10.1016/S0361-9230(97)00064-6",
language = "English",
volume = "43",
pages = "447--455",
journal = "Brain Research Bulletin",
issn = "0361-9230",
number = "5",

}

Neurotoxicity, blood-brain barrier breakdown, demyelination and remyelination associated with NMDA-induced lesions of the rat lateral hypothalamus. / Brace, Helen; Latimer, Mary; Winn, Philip.

In: Brain Research Bulletin, Vol. 43, No. 5, 01.06.1997, p. 447-455.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neurotoxicity, blood-brain barrier breakdown, demyelination and remyelination associated with NMDA-induced lesions of the rat lateral hypothalamus

AU - Brace, Helen

AU - Latimer, Mary

AU - Winn, Philip

PY - 1997/6/1

Y1 - 1997/6/1

N2 - Excitotoxins have been widely used to make lesions in the brains of experimental animals because they have the ability to destroy neurones while sparing fibres of passage. Because loss of fibres of passage can confound the interpretation of lesion effects, this property is of considerable value. Recently, however, there have been reports indicating that excitotoxins acting at different sites within the rat CNS not only destroy neurones but also strip myelin from fibres and compromise the integrity of the blood- brain barrier. However, some reports also indicate that the myelin content of the lesioned area recovers. Excitotoxic lesions of the lateral hypothalamus have been shown to produce local demyelination. The present studies sought to investigate this effect further by (1) defining the time course of demyelination and possible remyelination after excitotoxic lesions of the lateral hypothalamus made with N-methyl-D-aspartate (NMDA); (2) establishing the relationships between neuronal loss, de- and remyelination after various doses of NMDA; and (3) examining the integrity of the blood-brain barrier using an immunohistochemical probe. Our data show that after injection of NMDA into the lateral hypothalamus there was neuronal loss, blood-brain barrier disruption (followed by recovery over approximately 12 days), triggering of reactive gliosis, invasion of the lesioned area by cells from outwith the CNS, demyelination over an area coexistent with but not exceeding the area of neuronal loss, and remyelination. Remyelination occurred over a period of 3 months following the production of the lesion and was associated initially with blood vessels. It occurred across the whole of the lesioned area, not by encroachment from the borders. All doses of NMDA that produced neuronal death also produced demyelination. These data confirm that excitotoxic lesions of the lateral hypothalamus demyelinate fibres, but show for the first time that remyelination occurs here. They are consistent with reports concerning excitotoxin actions at other CNS sites and indicate that de- and remyelination after excitotoxic lesions is a ubiquitous process. Consideration should be given to this when using excitotoxins to make fibre- sparing lesions.

AB - Excitotoxins have been widely used to make lesions in the brains of experimental animals because they have the ability to destroy neurones while sparing fibres of passage. Because loss of fibres of passage can confound the interpretation of lesion effects, this property is of considerable value. Recently, however, there have been reports indicating that excitotoxins acting at different sites within the rat CNS not only destroy neurones but also strip myelin from fibres and compromise the integrity of the blood- brain barrier. However, some reports also indicate that the myelin content of the lesioned area recovers. Excitotoxic lesions of the lateral hypothalamus have been shown to produce local demyelination. The present studies sought to investigate this effect further by (1) defining the time course of demyelination and possible remyelination after excitotoxic lesions of the lateral hypothalamus made with N-methyl-D-aspartate (NMDA); (2) establishing the relationships between neuronal loss, de- and remyelination after various doses of NMDA; and (3) examining the integrity of the blood-brain barrier using an immunohistochemical probe. Our data show that after injection of NMDA into the lateral hypothalamus there was neuronal loss, blood-brain barrier disruption (followed by recovery over approximately 12 days), triggering of reactive gliosis, invasion of the lesioned area by cells from outwith the CNS, demyelination over an area coexistent with but not exceeding the area of neuronal loss, and remyelination. Remyelination occurred over a period of 3 months following the production of the lesion and was associated initially with blood vessels. It occurred across the whole of the lesioned area, not by encroachment from the borders. All doses of NMDA that produced neuronal death also produced demyelination. These data confirm that excitotoxic lesions of the lateral hypothalamus demyelinate fibres, but show for the first time that remyelination occurs here. They are consistent with reports concerning excitotoxin actions at other CNS sites and indicate that de- and remyelination after excitotoxic lesions is a ubiquitous process. Consideration should be given to this when using excitotoxins to make fibre- sparing lesions.

KW - blood-brain barrier

KW - demyelination

KW - excitotoxin

KW - lateral hypothalamus

KW - N- methyl-D-aspartate

KW - remyelination

KW - neurotoxicity

KW - n methyl dextro aspartic acid

KW - animal tissue

KW - hypothalamus nucleus

KW - pathophysiology

KW - myelin sheath

UR - http://www.scopus.com/inward/record.url?scp=0030877524&partnerID=8YFLogxK

U2 - 10.1016/S0361-9230(97)00064-6

DO - 10.1016/S0361-9230(97)00064-6

M3 - Article

VL - 43

SP - 447

EP - 455

JO - Brain Research Bulletin

JF - Brain Research Bulletin

SN - 0361-9230

IS - 5

ER -