In a related editorial, Anne Cross (Washington University, St Louis, Missouri, USA) and Emmanuelle Waubant (University of California, San Francisco, USA) describe KIR4.1 as "an unexpected but plausible antigenic target."
They note that while autoantibodies do not play a primary role in MS pathology, they may perpetuate the breakdown of the CNS, which is a hallmark of the disease.
http://www.medwire-news.md/44/100597/Ne ... rosis.html
In this research, in cytotoxic edema, KIR4.1 becomes "mislocalized." Perhaps it is the involvement of this protein in the break of the blood brain barrier which creates the immune reaction for some in MS, when KIR4.1 appears in brain tissue.
We see a reaction towards KIR4.1 in the brain with hydrocephalus and edema.
KIR4.1 is a protein which is involved in "water flux" or water transport.
In normal brain tissue, AQP4 and Kir4.1 were detected around the microvessels. In pathological brain tissue, AQP4 was upregulated in astrocytes in oedematous regions and Kir4.1 was upregulated in astrocytes in damaged brain.
Hydrocephalus is characterized by impaired cerebrospinal fluid (CSF) flow with enlargement of the ventricular cavities of the brain and progressive damage to surrounding tissue. Bulk water movement is altered in these brains. We hypothesized that increased expression of aquaporins, which are water-permeable channel proteins, would occur in these brains to facilitate water shifts. We used quantitative (real-time) RT-PCR, Western blotting and immunohistochemistry to evaluate the brain expression of aquaporins (AQP) 1, 4, and 9 mRNA and protein in Sprague–Dawley rats rendered hydrocephalic by injection of kaolin into cistern magna. AQP4 mRNA was significantly up-regulated in parietal cerebrum and hippocampus 4 weeks and 9 months after induction of hydrocephalus (P < 0.05). Although Western blot analysis showed no significant change, there was more intense perivascular AQP4 immunoreactivity in cerebrum of hydrocephalic brains at 3–4 weeks after induction. We did not detect mRNA or protein changes in AQP1 (located in choroid plexus) or AQP9 (located in select neuron populations). Kir4.1, a potassium channel protein linked to water flux, exhibited enhanced immunoreactivity in the cerebral cortex of hydrocephalic rats; the perineuronal distribution was entirely different from that of AQP4. These results suggest that brain AQP4 up-regulation might be a compensatory response to maintain water homeostasis in hydrocephalus.
Users browsing this forum: ElliotB