Microdialysis as Clinical Evaluation of Therapeutic Hypothermia in Rat Subdural Hematoma Model

Abstract

Cerebral microdialysis (MD) is a fine laboratory technique which has been established for studying physiological, pharmacological, and pathological changes in the experimental studies of traumatic brain injury (TBI). This technique has also been well translated and widely applied to clinical bedside monitoring to provide pathophysiological analysis in severe TBI patients. The MD technique is thus well suited for straightforward translation from basic science to clinical application.In this chapter, we describe our evaluation of MD method in acute subdural hematoma (ASDH) rat model. With 100 kDa cut-off microdialysis membrane, we could measure several biomarkers such as ubiquitin carboxy hydrolase L1 (UCH-L1), a neuronal marker and glial fibrillary acidic protein (GFAP), and a glial marker in extracellular fluid. In this experiment, we could detect that the peak of extracellular UCH-L1 in the early hypothermia group was significantly lower than in the normothermia group. Also, in the late phase of reperfusion (>2.5 h after decompression), extracellular GFAP in the early hypothermia group was lower than in the normothermia. These data thus suggested that early, preoperatively induced hypothermia could mediate the reduction of neuronal and glial damage in the reperfusion phase of ischemia/reperfusion brain injury.Microdialysis allows for the direct measurement of extracellular molecules in an attempt to characterize metabolic derangements before they become clinically relevant. Advancements in technology have allowed for the bedside assay of multiple markers of ischemia and metabolic dysfunction, and the applications for traumatic brain injury have been well established. As clinicians become more comfortable with these tools their widespread use and potential for clinical impact with continue to rise.

Hypothermia for Patients Requiring Evacuation of Subdural Hematoma: A Multicenter Randomized Clinical Trial

“…To examine the effect of induced hypothermia on biomarker levels, we analyzed the plasma concentration over time and did not see a group difference in GFAP or UCH-L1 levels. Contrary to our findings, rodent TBI models have demonstrated a reduction in UCH-L1 levels with hypothermia treatment [ 41 , 42 ]. However, after cardiac arrest UCH-L1 levels did not differ between comatose patients with cardiac arrest maintained at 36 °C compared with those maintained at 33 °C [ 43 ].…”

Feasibility of Human Neural Stem Cell Transplantation for the Treatment of Acute Subdural Hematoma in a Rat Model: A Pilot Study

“…Details for the induction of subdural hematoma and performance of the decompression surgery have been described in our previous reports (16–20). Briefly, the scalp was incised on the midline, and a single burr hole of 3 mm in diameter was drilled 2 mm to the left of the sagittal suture and 3 mm behind the coronal suture (Figure 1A).…”