Brain capillaries and cholinergic neurons persist in organotypic brain slices in the absence of blood flow

Eur J Neurosci. 2003 Jul;18(1):85-94. doi: 10.1046/j.1460-9568.2003.02728.x.

Abstract

Angiogenesis plays an important role during development of the brain and under pathological conditions. The aim of the present study was to observe interaction of brain capillaries and cholinergic neurons in organotypic brain slices. Immunohistochemistry was used to visualize brain capillary-like structures (RECA-1 antigen) and cholinergic neurons (choline acetyltransferase). Under normal culture conditions, a very low number of brain capillaries was found in 2- and 4-week-old cortex brain slices. Treatment of slices with acidic medium (pH 6) or hyperthermia (42 degrees C) markedly enhanced the number of brain capillaries. Incubation with 10 ng/mL vascular endothelial growth factor only enhanced angiogenesis in more developed slices. Cholinergic neurons survived in slices of the basal nucleus of Meynert; however, hyperthermia but not acidosis markedly decreased their number. In coslices of the basal nucleus of Meynert and cortex (pretreated with acidic medium), a high number of RECA-1-positive capillaries and cholinergic neurons persisted and displayed strong nerve fibre growth of cholinergic fibres into the cortex. In conclusion, we have demonstrated that RECA-1-positive capillaries and cholinergic neurons can be studied in slice cultures in the absence of blood perfusion, and that this model could provide a system to study mechanisms involved in vascular dementia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Acidosis / pathology
  • Animals
  • Basal Nucleus of Meynert / blood supply
  • Basal Nucleus of Meynert / pathology
  • Biomarkers
  • Brain / pathology
  • Capillaries / pathology
  • Capillaries / physiology
  • Cerebral Cortex / blood supply
  • Cerebral Cortex / pathology
  • Cerebrovascular Circulation / physiology*
  • Coculture Techniques
  • Endothelial Growth Factors / metabolism
  • Fever / pathology
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lymphokines / metabolism
  • Neuroglia / metabolism
  • Neurons / physiology*
  • Organ Culture Techniques
  • Parasympathetic Nervous System / cytology
  • Parasympathetic Nervous System / pathology
  • Parasympathetic Nervous System / physiology*
  • Perfusion
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Biomarkers
  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Acetylcholinesterase