Extracellular glutamate and other amino acids in experimental intracerebral hemorrhage: An in vivo microdialysis study
To determine whether extracellular concentrations of glutamate and other amino acids are significantly elevated after intracerebral hemorrhage and, if so, the temporal characteristics of these changes. Although the role of excitotoxic amino acids, particularly that of glutamate, has been described in ischemic stroke and head trauma, no information exists regarding their possible contribution to the pathogenesis of neuronal injury in intracerebral hemorrhage.Design
Prospective, controlled, laboratory trial.Settings
Animal research laboratory.Subjects
Sixteen anesthetized New Zealand rabbits.Intervention
We introduced intracerebral hemorrhage in each of eight anesthetized New Zealand rabbits by injecting 0.4 mL of autologous blood under arterial pressure into the deep gray matter of the cerebrum.Measurements and Main Results
Extracellular fluid samples were collected from the perihematoma region and contralateral (right) hemisphere by in vivo microdialysis at 30-min intervals for 6 hrs. Corresponding samples were similarly collected from both hemispheres in each of eight control animals that underwent needle placement without introduction of a hematoma. Concentrations of amino acids (glutamate, aspartate, asparagine, glycine, taurine, and γ-aminobutyric acid) in the samples were measured by use of high-pressure liquid chromatography with fluorescence detection. Glutamate concentrations (mean ± sem) were significantly higher in the hemisphere ipsilateral to the hematoma than in the contralateral hemisphere (92 ± 22 pg/μL vs. 22 ± 6 pg/μL) at 30 mins after hematoma creation. A significant increase was observed at 30 mins posthematoma creation in the hemisphere ipsilateral to the hematoma compared with the baseline value. A nonsignificant increase in glutamate concentration persisted in the hemisphere ipsilateral to the hematoma, ranging from 134% to 187% of baseline value between 1 and 5 hrs after hematoma creation. In the hemisphere ipsilateral to the hematoma, a three-fold increase in the concentration of glycine was observed at 30 mins after hematoma creation compared with the baseline level (890 ± 251 pg/μL vs. 291 ± 73 pg/μL). There was a significant difference between the hemisphere ipsilateral to the hematoma compared with the ipsilateral (corresponding) hemisphere of the control group at 30 mins posthematoma (890 ± 251 pg/μL vs. 248 ± 66 pg/μL). A similar transient increase was observed in taurine and asparagine concentrations at 30 mins after hematoma creation, compared with baseline measurements. Taurine concentrations in the hemisphere ipsilateral to the hematoma were significantly higher than the ipsilateral hemisphere of the control group (622 ± 180 pg/μL vs. 202 ± 64 pg/μL) at 30 mins after hematoma creation.Conclusions
The present study suggests that glutamate and other amino acids accumulate transiently in extracellular fluids in the perihematoma region during the early period of intracerebral hemorrhage. The exact role of these amino acids in the pathogenesis of neuronal injury observed in intracerebral hemorrhage needs to be defined.