Neuronic autophagy contributes to p-connexin 43 degradation in hippocampal astrocytes following traumatic brain injury in rats.

Connexins, gap junction proteins, have short half­lives of only a few hours; therefore, degradation of these proteins can rapidly modulate their function. Autophagy is a type of degradation pathway that has been implicated in several diseases and was reported to be induced following traumatic brain injury (TBI). The aim of the present study was to investigate the involvement of neuronic autophagy in proteolysis of phosphorylated connexin 43 (p­Cx43) in hippocampal astrocytes following TBI in rats. Western blot analysis and immunofluorescence showed a TBI­induced increase in levels of astrocytic p­Cx43 following treatment with 3­methyladenine, an inhibitor of autophagy, in the hippocampus. Internalized gap junctions were observed in the neuronic cytoplasm using transmission electron microscopy. These results demonstrated that neuronic autophagy may regulate cellular levels of p­Cx43 in hippocampal astrocytes following TBI. This therefore indicated that the persistence of p­Cx43 accumulation was due to insufficient degradation capacity of constitutive autophagy.

Terson syndrome with no cerebral hemorrhage: A case report.

The present study reports the case of a 33-year-old male who presented with Terson syndrome with no cerebral hemorrhage secondary to traumatic brain injury (TBI). A computed tomography scan of the patient, who had sustained an impact injury to the right occipital region, showed no cerebral lesion. Ophthalmoscopy clearly demonstrated vitreous hemorrhage in both eye globes. Vitreous hemorrhage, which results from an abrupt increase in intracranial pressure (ICP), is associated with TBI. In this case, the visual disturbance was attributed to Terson syndrome secondary to TBI. Therefore, close ophthalmological and radiological evaluation is required in patients with TBI, in order to enable the diagnosis of Terson syndrome and an early vitrectomy.

Astrocytic p-connexin 43 regulates neuronal autophagy in the hippocampus following traumatic brain injury in rats.

Gap junctions are conductive channels formed by membrane proteins termed connexins, which permit the intercellular exchange of metabolites, ions and small molecules. Previous data demonstrated that traumatic brain injury (TBI) activates autophagy and increases microtubule­associated protein 1 light chain 3 (LC3) immunostaining predominantly in neurons. Although previous studies have identified several extracellular factors that modulate LC3 expression, knowledge of the regulatory network controlling LC3 in health and disease remains incomplete. The aim of the present study was to assess whether gap junctions control the in vivo expression of LC3 in TBI. Using a modified weight­drop device, adult male Sprague­Dawley rats (weight, 350­375 g) were subjected to TBI. Phosphorylated gap junction protein levels and LC3­â…¡ levels were quantified using western blot analysis. The spatial distribution of immunoreactivity for phosphorylated connexin 43 (p­CX43) and LC3­â…¡ was analyzed by immunofluorescence. The results showed that p­CX43 expression in the hippocampus reached a maximum level 6 h following injury. In addition, the immunoreactivity of p­CX43 was localized in the astrocytes surrounding pyramidal neurons. The LC3­â…¡ protein content remained at high levels 24 h following injury. Double immunolabeling demonstrated that LC3­II dots colocalized with the hippocampus pyramidal neurons. Furthermore, inhibition of p­CX43 reduced TBI­induced autophagy, according to western blot analysis. As astrocytic gap junction coupling is affected in various forms of brain injury, the results suggest that point gap junctions/connexins are important regulators of autophagy in the hippocampal neurons following TBI.