Journal of Neural Transmission

, Volume 118, Issue 1, pp 87–114 | Cite as

Cardiac arrest-induced regional blood–brain barrier breakdown, edema formation and brain pathology: a light and electron microscopic study on a new model for neurodegeneration and neuroprotection in porcine brain

  • Hari Shanker Sharma
  • Adriana Miclescu
  • Lars Wiklund
Original Article

Abstract

Brief cardiac arrest and survival is often associated with marked neurological alterations related to cognitive and sensory motor functions. However, detail studies using selective vulnerability of brain after cardiac arrest in animal models are still lacking. We examined selective vulnerability of five brain regions in our well-established cardiac arrest model in pigs. Using light and electron microscopic techniques in combinations with immunohistochemistry, we observed that 5, 30, 60 and 180 min after cardiac arrest results in progressive neuronal damage that was most marked in the thalamus followed by cortex, hippocampus, hypothalamus and the brain stem. The neuronal damages are largely evident in the areas showing leakage of serum albumin in the neuropil. Furthermore, a tight correlation was seen between neuronal damage and increase in brain water content and Na+ indicating vasogenic edema formation after cardiac arrest. Damage to myelinated fibers and loss of myelin as seen using Luxol fast blue and myelin basic protein (MBP) immunoreactivity is clearly evident in the brain areas exhibiting neuronal damage. Upregulation of GFAP positive astrocytes closely corresponds with neuronal damages in different brain areas after cardiac arrest. At the ultrastructural level, perivascular edema together with neuronal, glial and endothelia cell damages is frequent in the brain areas showing albumin leakage. Damage to both pre- and post-synaptic membrane is also common. Treatment with methylene blue, an antioxidant markedly reduced neuronal damage, leakage of albumin, overexpression of GFAP and damage to myelin following cardiac arrest. Taken together, these observations suggest that (a) cardiac arrest is capable to induce selective neuronal, glial and myelin damage in different parts of the pig brain, and (b) antioxidant methylene blue is capable to induce neuroprotection by reducing BBB disruption. These observations strongly suggest that the model could be used to explore new therapeutic agents to enhance neurorepair following cardiac arrest-induced brain damage for therapeutic purposes.

Keywords

Cardiac arrest Pig brain Neuronal damage Nissl stain Glial changes Astrocytes GFAP Myelin Luxol fast blue Myelin basic protein Edema Ultrastructure Endothelial cells Perivascular edema 

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Hari Shanker Sharma
    • 1
    • 2
  • Adriana Miclescu
    • 1
  • Lars Wiklund
    • 1
  1. 1.Laboratory of Cerebrovascular Research, Department of Surgical Sciences, Anesthesiology and Intensive Care MedicineUniversity HospitalUppsalaSweden
  2. 2.Docent in NeuroanatomyUppsala UniversityUppsalaSweden

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