Temperature Dependent Change of Apparent Diffusion Coefficient of Water in Normal and Ischemic Brain of Rats

Abstract

Summary: To identify the temperature dependent change of the apparent diffusion coefficient (ADC) of water in brain tissue, the ADC values of normal rat brain were measured over a range of body temperatures with moni toring of head temperature using a small water reference implanted under the temporalis muscle. An initial exper iment using thermocouples implanted into the cortex, caudate-putamen, temporalis muscle, and rectum demon strated that temperature in all regions were highly corre lated over a temperature range from 33 to 39°C. In an other group of normal rats, brain ADC values varied al most uniformly with body temperature over the temperature range 33-39°C, implying that brain ADC val ues accurately reflect changes in brain temperature. The Diffusion-weighted magnetic resonance imaging (DWI) is derived by measuring the translational movement (diffusion) of water molecules over a short interval (Le Bihan et al., 1986;. DWI can rapidly detect and localize focal brain injury as early as minutes after the onset of ischemia (Moseley et al., 1990a,b;Mintorovitch et al., 1991; Minematsu et al., 1992a,b). This method is a powerful tool for studying clinical and experi mental brain ischemia.Brain temperature is an important physiologic pa rameter that should be monitored during experi- Abbreviations used: ADC, apparent diffusion coefficient; CCA, common carotid artery; DWI, diffusion-weighted imaging; MCA, middle cerebral artery; MRI, magnetic resonance imag ing; NMDA, N-methyl-o-aspartate; ROI, region of interest. 383effects of focal ischemia and administration of the non competitive N-methyl-o-aspartate (NMDA) antagonist, CNS-1102, on ADC were also examined, using the suture middle cerebral artery (MCA) occlusion model while maintaining the body temperature at 37°C. ADC values and therefore brain temperature in the nonischemic and ischemic hemispheres were not affected by the drug. These experiments suggest that brain ADC measurement could be useful in animal studies and, potentially, in hu mans to assess the effects of pharmacologic intervention on brain temperature. Key Words: Middle cerebral artery occlusion-Brain temperature-Magnetic resonance im aging-Apparent diffusion coefficient-Diffusion map ping.

The N -Methyl- d -Aspartate Antagonist CNS 1102 Protects Cerebral Gray and White Matter From Ischemic Injury Following Temporary Focal Ischemia in Rats

“…Similar results have been reported on ischemic lesion size with the use of the same dose after permanent and temporary focal cerebral ischemia. 4,5 The main novel finding in this study is that CNS 1102 protects white matter structures such as axons and myelin from ischemic injury. This finding is of importance because it demonstrates that white matter damage after ischemia may be treatable and could be of particular clinical interest for the future treatment of lacunar strokes.…”

“…No significant difference in physiological parameters and weight loss was observed between the 2 groups during the experiment as it has been reported by other investigators. 4,5 Cerebral ischemia triggers an excessive release of glutamate, producing overstimulation of glutamate receptors, especially the NMDA receptor. The subsequent cellular Ca 2ϩ overload is generally thought to represent the "final common pathway," leading to necrotic cell death of neurons.…”

“…13 NMDA antagonists that prevent the Ca 2ϩ influx through NMDA receptor blockade of Ca 2ϩ channels have successfully been used to treat neuronal injury after experimental ischemia in vivo. [3][4][5][6] CNS 1102 (Cerestat) in particular is a wellinvestigated NMDA antagonist that has potent neuroprotective effects. 6 CNS 1102 in this study protected striatal and cortical neurons from temporary focal cerebral ischemia.…”

“…NMDA receptor antagonists such as MK 801 or CNS 1102 (Cerestat) protect gray matter from ischemic injury. [3][4][5][6] Cerebral white matter was shown to be sensitive to acute ischemia and can probably be protected by pharmacological intervention. 7 In contrast to gray matter, glutamate is not thought to play an important role in white matter ischemic injury.…”

Interleukin‐1 exacerbates focal cerebral ischemia and reduces ischemic brain temperature in the rat

“…Brain temperature in health correlates well with body temperature (12,13) but there is good evidence that brain temperature dissociates from body temperature during ischemia. Ischemic brain temperature falls by 1-2°C relative to rectal temperature in rodent models of focal cerebral ischemia with little change in the temperature of the nonischemic hemisphere (14,15).…”