Multiple Sites of Vasopressin Synthesis in the Injured Brain

Abstract

Previous studies have indicated that the primary targets for vasopressin actions on the injured brain are the cerebrovascular endothelium and astrocytes, and that vasopressin amplifies the posttraumatic production of proinflammatory mediators. Here, the controlled cortical impact model of traumatic brain injury in rats was used to identify the sources of vasopressin in the injured brain. Injury increased vasopressin synthesis in the hypothalamus and cerebral cortex adjacent to the posttraumatic lesion. In the cortex, vasopressin was predominantly produced by activated microglia/macrophages, and, to a lesser extent, by the cerebrovascular endothelium. These data further support the pathophysiological role of vasopressin in brain injury.

Vasopressin V1a and V1b Receptors: From Molecules to Physiological Systems

“…In stroke patients, mean 24-h plasma AVP levels are higher than in control subjects and correlate with the severity score of the neurological deficit and the mean size of the lesion (42). In a controlled cortical impact model of brain injury, AVP synthesis was increased in activated microglia and macrophages and in the hypothalamus and cerebral cortex adjacent to the posttraumatic lesion (477).…”

Selective vasopressin-1a receptor antagonist prevents brain edema, reduces astrocytic cell swelling and GFAP, V1aR and AQP4 expression after focal traumatic brain injury

“…Subsequent evidence highlighted the link between increased GFAP and concomitant elevation of AQP4 and V1a receptors (V1aR) (Verkman, 2009) that may respond to injury-induced discharge of the hormone arginine vasopressin (AVP). V1aR are the predominant AVP receptor subtype in the CNS and are widely distributed in neurons, cortical astrocytes, and endothelial cells (Hernando et al, 2001, Landgraf, 1992, Ostrowski et al, 1994, Szmydynger-Chodobska et al, 2011, Szot et al, 1994). AVP is elevated in serum and cerebrospinal fluid (CSF) in humans following TBI (Huang et al, 2008, Kleindienst et al, 2010, Sorensen et al, 1985), and centrally released AVP may be instrumental in the development of brain edema (Cserr and Latzkovits, 1992, Landgraf, 1992).…”

“…AVP is elevated in serum and cerebrospinal fluid (CSF) in humans following TBI (Huang et al, 2008, Kleindienst et al, 2010, Sorensen et al, 1985), and centrally released AVP may be instrumental in the development of brain edema (Cserr and Latzkovits, 1992, Landgraf, 1992). V1aR on astrocytes potentially facilitate the transport of water across astrocytic cell membranes providing a mechanism for cellular swelling and brain edema formation in TBI (Pascale et al, 2006, Szmydynger-Chodobska et al, 2004) (Latzkovits et al, 1993, Pascale et al, 2006, Szmydynger-Chodobska et al, 2011). Taken together, these data implicate AVP and the V1aR as potential mediators of cell swelling and subsequent fulminating edematous change following cerebral injury (Dickinson and Betz, 1992, Doczi et al, 1982, 1984, Latzkovits et al, 1993, Niermann et al, 2001, Raichle and Grubb, Jr., 1978, Vajda et al, 2001).…”

Arginine Vasopressin V1a Receptor-Deficient Mice Have Reduced Brain Edema and Secondary Brain Damage following Traumatic Brain Injury

“…Specifically, AVP production was found predominantly in the microglia and macrophages that are associated with cortical microvessels and-to a lesser degreein the cerebrovascular endothelium. 45 In addition to these findings, both AVP-containing axonal processes leading from the hypothalamus directly to the lateral ventricles 16 and AVP synthesis in the choroid plexus endothelium have been described, suggesting that AVP can be released into the CSF and modulate autocrine and/ or paracrine functions. 46 Taken together, these results suggest that AVP released from the posterior pituitary gland as well as centrally released AVP from microglia, macrophages and cerebrovascular endothelium may play a role in post-traumatic and post-ischemic pathophysiology.…”