Effect of hypervolaemic haemodilution on cerebral glutamate, glycerol, lactate and free radicals in heatstroke rats

Abstract

In the present study, we attempted to assess the mechanisms underlying the neuroprotective effect of hypervolaemic haemodilution in rat heatstroke. In anaesthetized rats treated with normal saline (NS) immediately after the onset of heatstroke induced by T (a) (ambient temperature) of 42 degrees C for 88 min, followed by T (a) of 24 degrees C for 12 min, the values for MAP (mean arterial pressure), ICP (intracranial pressure), CPP (cerebral perfusion pressure), CBF (cerebral blood blow), brain P O(2) (partial pressure of O(2)) and striatal glutamate, glycerol, lactate/pyruvate ratio, hydroxyl radicals and neuronal damage score were 42+/-3 mmHg, 33+/-3 mmHg, 9+/-3 mmHg, 109+/-20 BPU (blood perfusion units), 6+/-1 mmHg, 51+/-7 micromol/l, 24+/-3 micromol/l, 124+/-32, 694+/-22% of baseline and 2.25+/-0.05 respectively. In animals treated with 10% albumin immediately after the onset of heatstroke ( T (a) of 42 degrees C for 88 min), the values for MAP, ICP, CPP, CBF, brain P O(2) and striatal glutamate, glycerol, lactate/pyruvate ratio, hydroxyl radicals and neuronal damage score were 64+/-6 mmHg, 10+/-2 mmHg, 54+/-5 mmHg, 452+/-75 BPU, 15+/-2 mmHg, 3+/-2 micromol/l, 4+/-2 micromol/l, 7+/-3, 119+/-7% of baseline and 0.38+/-0.05 respectively. Apparently, the heatstroke-induced arterial hypotension, intracranial hypertension, cerebral hypoperfusion, cerebral ischaemia, brain hypoxia, increased levels of striatal glutamate, glycerol, lactate/pyruvate ratio and hydroxyl radicals, and increased striatal neuronal damage score values were all attenuated significantly by the induction of hypervolaemic haemodilution in rats immediately at the onset of heatstroke. These results demonstrate that the neuroprotective effect of hypervolaemic haemodilution is associated with a decrease in the elevation of glutamate, glycerol, lactate and free radicals in brain exposed to experimental heatstroke-induced cerebral ischaemia/hypoxia injury.

Resuscitation from experimental heatstroke by transplantation of human umbilical cord blood cells*

“…As shown by our previous findings (17,19,34,35), ischemic neuron damage in different brain structures occurred 10 -15 mins after the onset of heatstroke. The heatstroke-induced neuron damage in different brain structures was reduced by intravenous infusion of albumin (19) or HUCBCs (present study) as well as brain cooling (34,35), initiated immediately after the onset of heatstroke.…”

“…The heatstroke-induced neuron damage in different brain structures was reduced by intravenous infusion of albumin (19) or HUCBCs (present study) as well as brain cooling (34,35), initiated immediately after the onset of heatstroke. Apparently, this histopathologic profile was noted in rats killed 12-15 mins after the onset of heatstroke.…”

“…Under urethane anesthesia, each animal was placed in a stereotaxic apparatus, and the combined probe was implanted into the striatum with use of the atlas and coordinates of Paxinos and Watson (18). The detailed procedures for measurement of brain temperature, PO 2 , and temperature were described previously (3,19).…”

Ischemic and Oxidative Damage to the Hypothalamus May Be Responsible for Heat Stroke

“…An increase in c-fos mRNA and protein in different brain regions, including the hypothalamus, the thalamus, and the amygdala, occurs in heat-exposed rats [19]. Large releases of hippocampal norepinephrine [20], hypothalamic dopamine and serotonin [21], and striatal glutamate [22] have also been reported. The hypothalamo-pituitary-adrenocortical (HPA) axis is also mobilized, as suggested by the increase in c-fos-positive cells [23] and c-fos mRNA content [24] in the hypothalamic paraventricular nucleus (PVN), as well as by the increase in blood adrenocorticotrophic-hormone (ACTH) and corticosterone concentrations [25, 26].…”

Clinical biochemistry of hyperthermia

“…In animal studies, cerebral glycerol, glutamate and lactate to pyruvate ratio is significantly elevated in rats with heatstroke compared with normal controls. 83 …”