Following Brain Trauma, Copeptin, a Stable Peptide Derived from the AVP Precusor, Does Not Reflect Osmoregulation but Correlates with Injury Severity

Abstract

The incidence of water and electrolyte disturbances following traumatic brain injury (TBI) is considerable and has been attributed to a dysregulation of the hypothalamic peptide arginine-vasopressin (AVP). Copeptin, the C-terminal part of the AVP prohormone, reflects AVP activity. In 71 TBI patients we measured copeptin in serum by a sandwich immunoassay. Injury severity was assessed by Glasgow Coma Score (GCS) and computed tomography, and recovery by Glasgow Outcome Score (GOS). Neuroendocrine and osmoregulation regulation were examined on day 0, 3 and 7, and 24 months post-injury. Copeptin was highest on admission (40.0 +/- 72.3 pmol/l), stabilized on day 3 and 7 (21.2 +/- 18.3 resp. 20.3 +/- 17.1 pmol/l), and normalized at follow-up (4.2 +/- 1.7 pmol/l). On admission, there was a correlation between serum sodium and urine excretion (p = 0.003), but the correlation got lost on day 3 and 7. Copeptin did not reflect the individual 24 h urine excretion or serum sodium levels indicating an uncoupling of copeptin/AVP release and renal water excretion. High copeptin level on day 3 were correlated with a low GCS (p < 0.001), midline shift (p = 0.019), intracerebral hemorrhage (p = 0.026), SAPS score (p = 0.001), as well as with a low GOS (p = 0.031). Copeptin was significantly decreased following skullbase fracture (p = 0.016).Our data reveal a loss of hypothalamic osmoregulation following TBI. The measurement of Copeptin/AVP release reveals a significant predictive function for the severity of TBI.

Stable Precursor Fragments of Vasoactive Peptides in Umbilical Cord Blood of Term and Preterm Infants

“…CT-proAVP has been the subject of several trials in the last years both as a prognostic and diagnostic marker in a wide range of diseases. As a prognostic marker, it was an independent predictor of survival in critically ill patients suffering from hemorrhagic and septic shock [16], ischemic stroke [17] and brain trauma [18]. In contrast, we found no correlation between any of the tested prohormones and neurological outcome or early-onset sepsis.…”

Copeptin Is Associated With Mortality in Patients With Traumatic Brain Injury

“…In accordance with this hypothesis, an earlier study showed a correlation between the severity of head injury and copeptin levels on admission. 11 Overall, our data suggest that copeptin level in this early period might reflect the initial hemorrhagic insult (as demonstrated by the close relationship between copeptin and GCS score).…”

“…[1][2][3][4][5][6][7] Moreover, copeptin levels have also been found to be elevated in ischemic 8,9 and hemorrhagic stroke 10 ; in these groups of patients, high copeptin levels were highly predictive for poor function outcome and mortality. Recently, Kleindienst et al 11 studied copeptin in brain trauma patients; in this context, copeptin levels increased with increasing severity of brain injury. However, no published information exists to date about the correlation of copeptin with mortality after traumatic brain injury (TBI).…”

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

“…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). 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).…”