Increased expression of vasopressin v1a receptors after traumatic brain injury.

Experimental evidence obtained in various animal models of brain injury indicates that vasopressin promotes the formation of cerebral edema. However, the molecular and cellular mechanisms underlying this vasopressin action are not fully understood. In the present study, we analyzed the temporal changes in expression of vasopressin V1a receptors after traumatic brain injury (TBI) in rats. In the intact brain, the V1a receptor was expressed in neurons located in all layers of the frontoparietal cortex. The V1a receptor-immunoreactive product was predominantly localized to neuronal nuclei and had both a diffused and punctate staining pattern. The V1a receptors were also expressed in astrocytes, especially in layer 1 of the frontoparietal cortex. In these cells, two distinctive patterns of immunopositive staining for V1a receptors were observed: a diffused cytosolic staining of cell bodies and processes and a clearly punctate staining pattern that was predominantly localized to the astrocytic cell bodies. The real-time reverse-transcriptase polymerase chain reaction analysis of changes in mRNA for the V1a receptor demonstrated that after TBI, there is an early (4 h post-TBI) increase in the number of transcripts in the ipsilateral frontoparietal cortex, when compared to the contralateral hemisphere or the sham-injured rats. This increase in the message was followed by the up-regulation of expression of the V1a receptors at the protein level. This was most evident in cortical astrocytes in the areas surrounding the lesion. The number of the V1a receptor-immunopositive astrocytes in the traumatized parenchyma gradually increased, starting at 8 h and peaking at 4-6 days after TBI. Furthermore, a redistribution of V1a receptors from the astrocytic cell bodies to the astrocytic processes was observed. In addition to astrocytes, an increased expression of V1a receptors was found in the endothelium of both blood microvessels and the large-diameter blood vessels in the frontoparietal cortex ipsilateral to injury. This increase in the V1a receptor expression was apparent between 2 and 4 days after TBI. As early as 1-2 h following the impact, there was also a striking increase in the number of the V1a receptor-immunopositive beaded axonal processes, with greatly enlarged varicosities, that were localized to various areas of the injured parenchyma. It is suggested that the increased expression of V1a receptors plays an important role in the vasopressin-mediated formation of edema in the injured brain.