Effect of vasopressin on cold-induced brain edema in cats

Abstract

Centrally released arginine vasopressin (AVP) has been implicated in the regulation of intracranial pressure (ICP) and brain water, and is elevated in the cerebrospinal fluid (CSF) of some patients with pseudotumor cerebri or subarachnoid hemorrhage. The authors have examined the relationship of AVP levels in CSF to ICP and brain water content in three experimental groups of cats with and without cold-induced vasogenic edema. With the cats under general anesthesia, a cold lesion was made and cannulas were placed in the cisterna magna, lateral ventricle, and aorta. Subsequent central and systemic measurements were made while the animals were awake and free-roaming. In Experiment 1, endogenous AVP levels in CSF were measured every 12 hours over a 48-hour period by radioimmunoassay in cats with sham craniotomy, mild edema, or moderate edema; no significant difference was found between groups although a diurnal variation was seen (range 2 to 18 pg/ml). In Experiment 2, either carrier solution or AVP, in doses of 1.5 or 30 ng, was administered via a lateral ventricle every 2 hours over 24 hours in unlesioned cats. In Experiment 3, cats received 2 or 35 ng of carrier solution or AVP in a similar manner, but coupled with a cold lesion. The CSF AVP levels ranged from an average of 100 to 681 pg/ml and 1.4 to 11.9 ng/ml in the two dose groups in both experiments. Neither the low nor the high dose had an effect on brain water content in normal white matter (Experiment 2), but both doses increased brain water content in edematous white matter (p less than 0.05 in Experiment 3), as determined by wet and dry weight measurements of standardized pieces of white matter. The ICP was decreased by high-dose AVP in normal cats (p less than 0.01 at 24 hours), but in lesioned cats was unchanged by low-dose and increased by high-dose AVP (p less than 0.05 at 18 hours). The authors conclude that pharmacological doses of central AVP facilitate the production of vasogenic edema.

Role of Arginine Vasopressin V1 and V2 Receptors for Brain Damage After Transient Focal Cerebral Ischemia

“…Our results are well in agreement with other experimental studies showing that AVP is involved in the pathophysiology of acute brain damage, for example, after subarachnoid or intracerebral hemorrhage (Doczi et al, 1984;Rosenberg et al, 1992), cortical focal lesions (Reeder et al, 1986;Bemana and Nagao, 1999), traumatic brain injury (Armstead, 2001), global cerebral ischemia (Liu et al, 1991(Liu et al, , 1996Ikeda et al, 1997), and permanent focal cerebral ischemia (Dickinson and Betz, 1992;Shuaib et al, 2002). The amount of AVP mRNA and of AVP protein increase after experimental cerebral ischemia (Liu, 1992;Liu et al, 2000) and levels of AVP are elevated in the CSF of stroke patients (Barreca et al, 2001).…”

“…In the Brattleboro rat, which does not express AVP, brain sodium uptake was reduced during hypernatremia and after cerebral ischemia by 61% and 36%, respectively, and brain edema formation was reduced by 1/3 (DePasquale et al, 1989;Dickinson and Betz, 1992) while all changes were reversible when AVP was administered intracerebroventricularly (Dickinson and Betz, 1992). Most interestingly, AVP seems to influence brain edema formation after both cold injury and global cerebral ischemia, two conditions known to be associated almost exclusively with the development of vasogenic or cytotoxic brain edema, respectively (Reeder et al, 1986;Liu et al, 1996). These findings indicate that AVP may influence brain water and brain volume homeostasis by multiple pathways, for example, by influencing the permeability of the BBB and by directly modulating the cell volume of neurons and astrocytes.…”

“…Although intracerebroventricular infusion of AVP does not alter brain water content in normal brain, it does significantly increase brain edema formation and cerebral sodium uptake during hypernatremia (Vajda et al, 2001), after cold injury-induced brain edema (Reeder et al, 1986), and after postischemic brain edema (Liu et al, 1996). In the Brattleboro rat, which does not express AVP, brain sodium uptake was reduced during hypernatremia and after cerebral ischemia by 61% and 36%, respectively, and brain edema formation was reduced by 1/3 (DePasquale et al, 1989;Dickinson and Betz, 1992) while all changes were reversible when AVP was administered intracerebroventricularly (Dickinson and Betz, 1992).…”

Attenuated Development of Ischemic Brain Edema in Vasopressin-Deficient Rats

“…Pharmacologic doses of vasopressin delivered into the CSF or brain parenchyma have been shown to induce increases in brain water in the absence of cerebral injury (D6czi et aI., 1982;Rosenberg et aI., 1988;Rosenberg et aI., 1990). Reeder et al (1986) showed that vasopressin en hanced white matter edema formation following cold-induced injury, and DePasquale et aI., (1989) showed that hypernatremia-induced brain volume regulation was attenuated in vasopressin defi ciency. In our model of partial ischemic injury, we demonstrated that vasopressin deficiency attenu ated edema formation and that intraventricular re- placement of vasopressin normalized edema forma tion.…”

“…This correlation had led to investigations concerning the role of vasopressin in brain edema formation. Although one study has demonstrated that edema formation from a cold-induced brain in jury is accelerated following intraventricular admin istration of pharmacologic doses of vasopressin (Reeder et al, 1986), it is not known whether re lease of endogenous vasopressin accelerates edema formation.…”