Failure of hyperthermia to open rat blood-brain barrier: Reduced permeation of sucrose

Summary

To determine if near-lethal elevation of body temperature opens the blood-brain barrier,¹⁴C-sucrose or¹²⁵I-bovine serum albumin was injected intravenously into anesthetized, normothermic rats (37–38° C) or rats in which hyperthermia (>41° C) was induced and maintained by whole-body exposure toxinfrared or 2,450 MHz microwave radiation. Blood-brain barrier opening was sought as an increase in cerebrovascular permeability-area product (PA), calculated as the ratio of radiotracer concentration accumulated in brain parenchyma 25 or 30 min after injection (dpm·g⁻¹) relative to the time-averaged concentration in arterial plasma sampled throughout the same time period (dpm·s·ml⁻¹). The following profiles of elevated body-core temperature (°C) vs time did not cause barrier opening: 41.5–42.0 (range) during 40 min of infrared exposure (sucrose tested); 41.0–41.3 increasing to 41.9–42.3 during 33 min of microwave exposure (sucrose); 41.0–41.6 during 2.5 h of infrared or microwave exposure (albumin tested). In sucrose experiments, hyperthermia greatly elevated the profile of plasma sucrose concentration vs time compared to that for control rats injected with the same dose. However, parenchymal uptake of sucrose did not increase proportionally so that mean PA values for different brain regions were 45–77% lower than control values. Hyperthermia caused an apparent reduction in permeation of sucrose across the blood-brain barrier.