Brain temperature homeostasis: physiological fluctuations and pathological shifts

Abstract

Brain temperature is a physiological parameter, reflecting the balance between metabolism-related intra-brain heat production and heat loss by cerebral circulation to the rest of the body and then to the external environment. First, we present data on brain temperature fluctuations occurring under physiological and behavioral conditions and discuss their mechanisms. Since most processes governing neural activity are temperature-dependent, we consider how naturally occurring temperature fluctuations could affect neural activity and neural functions. We also consider psychomotor stimulants and show that their hyperthermic effects are state-dependent and modulated by environmental conditions. Since high temperature could irreversibly damage neural cells and worsen various pathological processes, we consider the situations associated with pathological brain hyperthermia and evaluate its role in acute perturbations of brain functions, neurotoxicity, and neurodegeneration. We also discuss the limitations in consideration of brain temperature within the frameworks of physiological regulation and homeostasis. While different adaptive mechanisms could, within some limits, compensate for altered intra-brain heat balance, these mechanisms could fail in real-life situations, resulting in life-threatening health complications.

Figure 1

Changes in brain (NAcc, dorsal striatum and hippocampus) and arterial blood temperature induced by 3-min tail-pinch in awake, freely moving male rats. A shows mean (±sem) values of absolute temperatures (°C); B shows differentials between relative temperature changes in each brain structure and in arterial blood; C shows rapid-time course resolution of temperature changes (2 s). Filled symbols in each graph indicate values significantly different from baseline. Vertical hatched lines show onset and offset of tail-pinch. For additional details see .

Figure 2

Changes in brain (NAcc), muscle (musculus temporalis) and skin temperatures induced in male rats by tail-pinch (left panel) and social interaction with female (right panel). A shows relative temperature changes; B shows NAcc-muscle and skin-muscle temperature differentials, and C shows locomotion. Vertical hatched lines in each graph show onset of stimulation and filled symbols denote values significantly different from pre-stimulus baseline. For additional details see .

Figure 3

Relationships between changes in brain temperature induced in rats by various arousing stimuli [intraperitoneal (ip) and subcutaneous (sc) injections of saline (0.2 ml), social interaction with female rat, 3-min tail-pinch and exposure of sexually-experienced males to females] and basal brain temperature. Each graph shows dependence of NAcc temperature change induced by a stimulus from pre-stimulus basal NAcc temperatures. In each case, temperature elevation was negatively correlated with basal temperature (each graph shows regression lines, regression equations and coefficients of correlation, r). Original data were previously published (21, 90).

Figure 4

Changes in brain (nucleus accumbens or NAcc and hippocampus or Hippo) and temporal muscle temperatures induced in male rats by methamphetamine (9 mg/kg) administered under different environmental conditions. Left panel shows the effects in quiet resting conditions at normal ambient temperatures (23°C), middle panel shows the effects under conditions of physiological activation (interaction with female started 30-min before drug injection; shown as first hatched line), and right panel shows the effects in warm environmental conditions (29°C). The moment of drug injection is shown by vertical hatched line at 0 min. Graphs in left and central panels represent absolute (A) and relative temperature (B) changes as well as brain-muscle differentials (C). Filled symbols mark values significantly different from baseline. Since most rats exposed to METH at 29°C died during the experiment, mean temperature data for this group (right panel) are shown only for the period when all rats were alive (A, relative temperature change; B, brain-muscle temperature. C in this panel shows temperature dynamics in all experimental rats hours 5 hours following drug injection. Four rats (,, and 6) that showed robust hyperthermia (41–42.5°C) died between 2 and 3 hours post-injection. Another rat (1) that survived the period of recording died over-night. For other details see , .

Figure 5

Temperature dependence of albumin imminoreactivity and cellular brain abnormalities. Data (the cell counts within the same areas within well-defined anatomical structures) are shown for the brain as a whole (A; open circle show original data and closed circle show mean averages), individual brain structures (B), and individual cortical areas (C). For details see the text.

Figure 6

Temperature dependence of tissue water shown separately for cortex and thalamus. Horizontal hatched lines show “normal” values evaluated in brains of awake, drug-free rats at normothermia. Vertical hatched lines show limits of “normal” brain temperature. In both structure, tissue water content was directly and strongly dependent on brain temperature (regression lines, regression equations, and coefficients of correlation are shown for the cortex). For details see the text.

Figure 7

Correlative relationships between individual brain parameters assessed in urethane-anesthetized rats passively warmed to different brain temperatures. A shows the relationships between numbers of albumin-positive cells and tissue water evaluated separately in the cortex and thalamus. B shows the relationships between the numbers of albumin-positive and morphologically abnormal cells evaluated in the brain as a whole. C shows the relationships between tissue water content and amounts of morphologically abnormal cells evaluated separately in the cortex and thalamus. Each graph contains coefficients of correlation and regression lines. Hatched line in B shows a line of equality. Each correlation coefficient value is highly significant (p<0.001). For additional details see the text.