Relationship Between Injured Cingulum and Impaired Consciousness in Patients with Hypoxic-Ischemic Brain Injury

Objectives We investigated the relationship between cingulum injury and impaired consciousness in patients with hypoxic-ischemic brain injury (HI-BI) by using diffusion tensor tractography (DTT). Methods We recruited 29 patients with HI-BI and 25 normal control subjects. The patients were classified as intact consciousness (group A, 13 patients) or impaired consciousness (group B, 16 patients). The DTT parameters of fractional anisotropy (FA) and tract volume (TV) were estimated for both cinguli. Glasgow Coma Scale (GCS) and Coma Recovery Scale-Revised (CRS-R) scores were also evaluated. Results The FA and TV values of the cinguli in groups A and B were lower than those of the control group (p < 0.05), and the FA and TV values of group B were lower than those of group A (p < 0.05). The FA and TV values of the cinguli in group A were not significantly correlated with GCS and CRS-R scores (p > 0.05); however, regarding the group B, the FA correlations with GCS (r = 0.457, p < 0.05) and CRS-R (r = 0.494, p < 0.05) and those of TV with GCS (r = 0.500, p < 0.05) and CRS-R (r = 0.491, p < 0.05) were moderately positive. Conclusions We found a significant relationship between injury of the cingulum and impaired consciousness in patients with HI-BI. Our results suggest that an injured cingulum could be an appropriate target for neurointervention or neurorehabilitation in patients with impaired consciousness following HI-BI.

C3a Receptor Signaling Inhibits Neurodegeneration Induced by Neonatal Hypoxic-Ischemic Brain Injury

Hypoxic-ischemic neonatal encephalopathy due to perinatal asphyxia is the leading cause of brain injury in newborns. Clinical data suggest that brain inflammation induced by perinatal insults can persist for years. We previously showed that signaling through the receptor for complement peptide C3a (C3aR) protects against cognitive impairment induced by experimental perinatal asphyxia. To investigate the long-term neuropathological effects of hypoxic-ischemic injury to the developing brain and the role of C3aR signaling therein, we subjected wildtype mice, C3aR deficient mice, and mice expressing biologically active C3a in the CNS to mild hypoxic-ischemic brain injury on postnatal day 9. We found that such injury triggers neurodegeneration and pronounced reactive gliosis in the ipsilesional hippocampus both of which persist long into adulthood. Transgenic expression of C3a in reactive astrocytes reduced hippocampal neurodegeneration and reactive gliosis. In contrast, neurodegeneration and microglial cell density increased in mice lacking C3aR. Intranasal administration of C3a for 3 days starting 1 h after induction of hypoxia-ischemia reduced neurodegeneration and reactive gliosis in the hippocampus of wildtype mice. We conclude that neonatal hypoxic-ischemic brain injury leads to long-lasting neurodegeneration. This neurodegeneration is substantially reduced by treatment with C3aR agonists, conceivably through modulation of reactive gliosis.