Heat-shock protein and c-fos expression in focal microvascular brain damage

Perttu J. Lindsberg, Kai U. Frerichs, Anna Leena Sirén, John M. Hallenbeck, Thaddeus Nowak

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Cortical brain damage was produced in rats by a focal pulse from a Nd-YAG laser, and evolution of the lesion was evaluated at 30 min, and 2, 8, and 24 h with respect to microvascular perfusion, blood-brain barrier (BBB) permeability, and expression of both the heat-shock/stress protein, hsp72, and the c-fos proto-oncogene transcription factor. A double-labeling fluorescence technique employing intravenously injected Evans blue albumin (EBA) and fluorescein-labeled dextran was used to map and measure BBB damage and microvascular perfusion in fresh frozen brain sections. Hsp72 and c-fos mRNAs were localized by in situ hybridization, and the respective proteins were identified by immunocytochemistry. Parallel sections were stained for glial fibrillary acidic protein and for routine histologic examination. Striking hsp72 mRNA expression was evident by 2 h in an ~300 μm wide rim surrounding an area of expanding BBB damage. Increased hsp72 mRNA was observed only in regions of preserved microcirculation, where the hsp72 protein was subsequently localized exclusively in the vasculature at 24 h after the insult, Hsp72-positive endothelial cells spanned the narrow margin between the lesion and histologically normal, glial fibrillary acidic protein (GFAP)-positive cortical tissue. There was no hsp72 expression in the area of subcortically migrating edema fluid. Inductions of c-fos mRNA and Fos protein were not strikingly evident around the focal brain lesion, but were observed transiently throughout the injured hemisphere at 30 min and 2.5 h, respectively, indicating that spreading depression was triggered by the focal injury. These results are in striking contrast to those previously obtained from studies of models of focal ischemic or traumatic brain injury, which are characterized by a complex pattern of glial and neuronal hsp72 expression in the periphery of an infarct, and which suggest that the tightly demarcated lesion produced by the Nd-YAG laser lacks these components of graded injury that are evident following other types of focal brain damage.

Original languageEnglish (US)
Pages (from-to)82-91
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Volume16
Issue number1
DOIs
StatePublished - Jan 1 1996

Fingerprint

Heat-Shock Proteins
Blood-Brain Barrier
Messenger RNA
Glial Fibrillary Acidic Protein
Solid-State Lasers
Brain
Perfusion
HSP72 Heat-Shock Proteins
fos Genes
Evans Blue
Wounds and Injuries
Frozen Sections
Microcirculation
Neuroglia
Brain Injuries
In Situ Hybridization
Pulse
Albumins
Permeability
Edema

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Heat-shock protein and c-fos expression in focal microvascular brain damage. / Lindsberg, Perttu J.; Frerichs, Kai U.; Sirén, Anna Leena; Hallenbeck, John M.; Nowak, Thaddeus.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 16, No. 1, 01.01.1996, p. 82-91.

Research output: Contribution to journalArticle

Lindsberg, Perttu J. ; Frerichs, Kai U. ; Sirén, Anna Leena ; Hallenbeck, John M. ; Nowak, Thaddeus. / Heat-shock protein and c-fos expression in focal microvascular brain damage. In: Journal of Cerebral Blood Flow and Metabolism. 1996 ; Vol. 16, No. 1. pp. 82-91.
@article{600dd7d06b7a48e6993c682f668de469,
title = "Heat-shock protein and c-fos expression in focal microvascular brain damage",
abstract = "Cortical brain damage was produced in rats by a focal pulse from a Nd-YAG laser, and evolution of the lesion was evaluated at 30 min, and 2, 8, and 24 h with respect to microvascular perfusion, blood-brain barrier (BBB) permeability, and expression of both the heat-shock/stress protein, hsp72, and the c-fos proto-oncogene transcription factor. A double-labeling fluorescence technique employing intravenously injected Evans blue albumin (EBA) and fluorescein-labeled dextran was used to map and measure BBB damage and microvascular perfusion in fresh frozen brain sections. Hsp72 and c-fos mRNAs were localized by in situ hybridization, and the respective proteins were identified by immunocytochemistry. Parallel sections were stained for glial fibrillary acidic protein and for routine histologic examination. Striking hsp72 mRNA expression was evident by 2 h in an ~300 μm wide rim surrounding an area of expanding BBB damage. Increased hsp72 mRNA was observed only in regions of preserved microcirculation, where the hsp72 protein was subsequently localized exclusively in the vasculature at 24 h after the insult, Hsp72-positive endothelial cells spanned the narrow margin between the lesion and histologically normal, glial fibrillary acidic protein (GFAP)-positive cortical tissue. There was no hsp72 expression in the area of subcortically migrating edema fluid. Inductions of c-fos mRNA and Fos protein were not strikingly evident around the focal brain lesion, but were observed transiently throughout the injured hemisphere at 30 min and 2.5 h, respectively, indicating that spreading depression was triggered by the focal injury. These results are in striking contrast to those previously obtained from studies of models of focal ischemic or traumatic brain injury, which are characterized by a complex pattern of glial and neuronal hsp72 expression in the periphery of an infarct, and which suggest that the tightly demarcated lesion produced by the Nd-YAG laser lacks these components of graded injury that are evident following other types of focal brain damage.",
author = "Lindsberg, {Perttu J.} and Frerichs, {Kai U.} and Sir{\'e}n, {Anna Leena} and Hallenbeck, {John M.} and Thaddeus Nowak",
year = "1996",
month = "1",
day = "1",
doi = "10.1097/00004647-199601000-00010",
language = "English (US)",
volume = "16",
pages = "82--91",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Heat-shock protein and c-fos expression in focal microvascular brain damage

AU - Lindsberg, Perttu J.

AU - Frerichs, Kai U.

AU - Sirén, Anna Leena

AU - Hallenbeck, John M.

AU - Nowak, Thaddeus

PY - 1996/1/1

Y1 - 1996/1/1

N2 - Cortical brain damage was produced in rats by a focal pulse from a Nd-YAG laser, and evolution of the lesion was evaluated at 30 min, and 2, 8, and 24 h with respect to microvascular perfusion, blood-brain barrier (BBB) permeability, and expression of both the heat-shock/stress protein, hsp72, and the c-fos proto-oncogene transcription factor. A double-labeling fluorescence technique employing intravenously injected Evans blue albumin (EBA) and fluorescein-labeled dextran was used to map and measure BBB damage and microvascular perfusion in fresh frozen brain sections. Hsp72 and c-fos mRNAs were localized by in situ hybridization, and the respective proteins were identified by immunocytochemistry. Parallel sections were stained for glial fibrillary acidic protein and for routine histologic examination. Striking hsp72 mRNA expression was evident by 2 h in an ~300 μm wide rim surrounding an area of expanding BBB damage. Increased hsp72 mRNA was observed only in regions of preserved microcirculation, where the hsp72 protein was subsequently localized exclusively in the vasculature at 24 h after the insult, Hsp72-positive endothelial cells spanned the narrow margin between the lesion and histologically normal, glial fibrillary acidic protein (GFAP)-positive cortical tissue. There was no hsp72 expression in the area of subcortically migrating edema fluid. Inductions of c-fos mRNA and Fos protein were not strikingly evident around the focal brain lesion, but were observed transiently throughout the injured hemisphere at 30 min and 2.5 h, respectively, indicating that spreading depression was triggered by the focal injury. These results are in striking contrast to those previously obtained from studies of models of focal ischemic or traumatic brain injury, which are characterized by a complex pattern of glial and neuronal hsp72 expression in the periphery of an infarct, and which suggest that the tightly demarcated lesion produced by the Nd-YAG laser lacks these components of graded injury that are evident following other types of focal brain damage.

AB - Cortical brain damage was produced in rats by a focal pulse from a Nd-YAG laser, and evolution of the lesion was evaluated at 30 min, and 2, 8, and 24 h with respect to microvascular perfusion, blood-brain barrier (BBB) permeability, and expression of both the heat-shock/stress protein, hsp72, and the c-fos proto-oncogene transcription factor. A double-labeling fluorescence technique employing intravenously injected Evans blue albumin (EBA) and fluorescein-labeled dextran was used to map and measure BBB damage and microvascular perfusion in fresh frozen brain sections. Hsp72 and c-fos mRNAs were localized by in situ hybridization, and the respective proteins were identified by immunocytochemistry. Parallel sections were stained for glial fibrillary acidic protein and for routine histologic examination. Striking hsp72 mRNA expression was evident by 2 h in an ~300 μm wide rim surrounding an area of expanding BBB damage. Increased hsp72 mRNA was observed only in regions of preserved microcirculation, where the hsp72 protein was subsequently localized exclusively in the vasculature at 24 h after the insult, Hsp72-positive endothelial cells spanned the narrow margin between the lesion and histologically normal, glial fibrillary acidic protein (GFAP)-positive cortical tissue. There was no hsp72 expression in the area of subcortically migrating edema fluid. Inductions of c-fos mRNA and Fos protein were not strikingly evident around the focal brain lesion, but were observed transiently throughout the injured hemisphere at 30 min and 2.5 h, respectively, indicating that spreading depression was triggered by the focal injury. These results are in striking contrast to those previously obtained from studies of models of focal ischemic or traumatic brain injury, which are characterized by a complex pattern of glial and neuronal hsp72 expression in the periphery of an infarct, and which suggest that the tightly demarcated lesion produced by the Nd-YAG laser lacks these components of graded injury that are evident following other types of focal brain damage.

UR - http://www.scopus.com/inward/record.url?scp=0029671115&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029671115&partnerID=8YFLogxK

U2 - 10.1097/00004647-199601000-00010

DO - 10.1097/00004647-199601000-00010

M3 - Article

C2 - 8530560

AN - SCOPUS:0029671115

VL - 16

SP - 82

EP - 91

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 1

ER -