Intracranial pressure, cerebral blood flow, and cerebrospinal fluid formation during hyperammonemia in cat

Abstract

Intracranial pressure (ICP), cerebral blood flow (CBF), and the cerebrospinal fluid (CSF) formation rate were examined in anesthetized cats during ammonia intoxication. Hyperammonemia, evoked by intravenous infusion of ammonium acetate, caused a significant increase in ICP when the arterial blood ammonia level exceeded 400 mumol X liter-1. A progressive elevation of blood ammonia concentration was followed by a gradual rise in CBF, measured by the xenon-133 clearance technique. At an arterial blood ammonia level exceeding 500 mumol X liter-1, the CBF reached a plateau at 30% above the mean control value. Increase in ICP correlated weakly, but significantly, with the increase in CBF (R = 0.489, p less than 0.005). Elevation of the arterial blood ammonia level to 780.4 +/- 25.5 mumol X liter-1 for 2 hours elicited a significant gradual increase in CSF formation rate, measured by the ventriculocisternal perfusion method with iodine-125-albumin as an indicator substance. A maximum increase in CSF flow of 81% was noted at the end of the ammonium acetate infusion. It is suggested that hyperammonemia increases ICP both by cerebral vasodilatation and by enhancement of the CSF formation rate.

Mild hypothermia delays the onset of coma and prevents brain edema and extracellular brain glutamate accumulation in rats with acute liver failure

“…In favor of this hypothesis, administration of the glutamine synthetase inhibitor, methionine sulfoximine, reduces ammonia-induced brain edema both in vitro 27 and in vivo. 28,29 However, in the present study, hypothermia-induced reductions in brain-water content in ALF rats were not accompanied by significant reductions of extracellular brain glutamine at time points associated with brain edema. These findings suggest that mild hypothermia' s major protective effect on brain edema in this model of ALF is not mediated via an effect on brain glutamine synthesis.…”

Distinctly abnormal brain metabolism in late-onset ornithine transcarbamylase deficiency

“…21 Because astrocytes are rich in Gln synthetase, it has been suggested that ammonia-induced astrocyte Gln accumulation creates an osmotic gradient that causes a shift of water into the astrocytes, resulting in astrocyte swelling, cerebral edema, and increased intracranial pressure. 19,22 It was also demonstrated that the cerebral edema associated with hyperammonemia can be prevented by preventing Gln accumulation in the brain, suggesting that hyperammonemia is necessary but not sufficient to produce cerebral edema. 23 Supporting this hypothesis, the cerebrospinal Gln concentrations in patients with OTCD are extraordinarily high during hyperammonemic encephalopathy.…”

“…Because of the intimate relationship of the astrocyte processes with cerebral capillaries and venules, it is not surprising that alterations of cerebral blood flow are commonly found in experimental hyperammonemia. 18,19 We performed 1 HMRS in the normal-appearing posterior centrum semiovale in five of the six patients with OTCD. We could not completely exclude contamination of faint T2 prolongation and minimal CSF in Patient 1.…”

Hypothermia in Acute Liver Failure

“…It has been pro-posed that ammonia-induced brain edema in ALF involves alterations in astrocytic in-tracellular osmolarity resulting from glutamine accumulation (Cordoba et al, 1996). This is supported by studies demonstrating the administration of the glutamine synthetase inhibition, methionine sulfoximine, reduces ammonia-induced brain edema both in vitro (Norenberg and Bender, 1994) and in vivo (Chodobski et al, 1986;Takahashi et al, 1991). However, recently hypothermia-induced reductions in brain water content in ALF rats were not accompanied by significant reductions of microdialysate (extracellular) brain glutamine (Rose et al, 2000) or brain glutamine (Chatauret et al, 2003) at time points associated with brain edema.…”