Cortical astrogliosis and increased perivascular aquaporin-4 in idiopathic intracranial hypertension

Brain Res. 2016 Aug 1:1644:161-75. doi: 10.1016/j.brainres.2016.05.024. Epub 2016 May 14.

Abstract

The syndrome idiopathic intracranial hypertension (IIH) includes symptoms and signs of raised intracranial pressure (ICP) and impaired vision, usually in overweight persons. The pathogenesis is unknown. In the present prospective observational study, we characterized the histopathological changes in biopsies from the frontal brain cortical parenchyma obtained from 18 IIH patients. Reference specimens were sampled from 13 patients who underwent brain surgery for epilepsy, tumors or acute vascular diseases. Overnight ICP monitoring revealed abnormal intracranial pressure wave amplitudes in 14/18 IIH patients, who underwent shunt surgery and all responded favorably. A remarkable histopathological observation in IIH patients was patchy astrogliosis defined as clusters of hypertrophic astrocytes enclosing a nest of nerve cells. Distinct astrocyte domains (i.e. no overlap between astrocyte processes) were lacking in most IIH biopsy specimens, in contrast to their prevalence in reference specimens. Evidence of astrogliosis in IIH was accompanied with significantly increased aquaporin-4 (AQP4) immunoreactivity over perivascular astrocytic endfeet, compared to the reference specimens, measured with densitometry. Scattered CD68 immunoreactive cells (activated microglia and macrophages) were recognized, indicative of some inflammation. No apoptotic cells were demonstrable. We conclude that the patchy astrogliosis is a major finding in patients with IIH. We propose that the astrogliosis impairs intracranial pressure-volume reserve capacity, i.e. intracranial compliance, and contributes to the IIH by restricting the outflow of fluid from the cranium. The increased perivascular AQP4 in IIH may represent a compensatory mechanism to enhance brain fluid drainage.

Keywords: Aquaporin-4; Astrogliosis; Benign intracranial hypertension; Interstitial fluid disturbance; Pseudotumor cerebri; Pulsatile intracranial pressure.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aquaporin 4 / metabolism*
  • Astrocytes / metabolism*
  • Astrocytes / pathology*
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology*
  • Female
  • Gliosis / complications*
  • Humans
  • Male
  • Middle Aged
  • Neurons / metabolism
  • Neurons / pathology
  • Prospective Studies
  • Pseudotumor Cerebri / complications
  • Pseudotumor Cerebri / metabolism*
  • Pseudotumor Cerebri / pathology*
  • Young Adult

Substances

  • AQP4 protein, human
  • Aquaporin 4