Intraventricular injection of antibodies to β 1 -integrins generates pressure gradients in the brain favoring hydrocephalus development in rats

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 297; no. 5; pp. R1312 - R1321
• Main Authors: Nagra, Gurjit, Koh, Lena, Aubert, Isabelle, Kim, Minhui, Johnston, Miles
• Format: Journal Article
• Language: English
• Published: 01.11.2009
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00307.2009

In some tissues, the injection of antibodies to the β 1 -integrins leads to a reduction in interstitial fluid pressure, indicating an active role for the extracellular matrix in tissue pressure regulation. If perturbations of the matrix occur in the periventricular area of the brain, a comparable lowering of interstitial pressures may induce transparenchymal pressure gradients favoring ventricular expansion. To examine this concept, we measured periventricular (parenchymal) and ventricular pressures with a servo-null micropipette system (2-μm tip) in adult Wistar rats before and after anti-integrin antibodies or IgG/IgM isotype controls were injected into a lateral ventricle. In a second group, the animals were kept for 2 wk after similar injections and after euthanization, the brains were removed and assessed for hydrocephalus. In experiments in which antibodies to β 1 -integrins ( n = 10) but not isotype control IgG/IgM ( n = 7) were injected, we observed a decline in periventricular pressures relative to the preinjection values. Under similar circumstances, ventricular pressures were elevated ( n = 10) and were significantly greater than those in the periventricular interstitium. We estimated ventricular to periventricular pressure gradients of up to 4.3 cmH 2 O. In the chronic preparations, we observed enlarged ventricles in many of the animals that received injections of anti-integrin antibodies (21 of 29 animals; 72%) but not in any animal receiving the isotype controls. We conclude that modulation/disruption of β 1 -integrin-matrix interactions in the brain generates pressure gradients favoring ventricular expansion, suggesting a novel mechanism for hydrocephalus development.