Direct reprogramming of non-neuronal cells to generate new neurons is a promising approach to repair damaged brains. Impact of the in vivo environment on neuronal reprogramming, however, is poorly understood. Here we show that regional differences and injury conditions have significant influence on the efficacy of reprogramming and subsequent survival of newly generated neurons in the adult rodent brain. A combination of local exposure to growth factors and retrovirus-mediated overexpression of the neurogenic transcription factor Neurogenin2 (Neurog2) can induce new neurons from non-neuronal cells in the adult neocortex and striatum where neuronal turnover is otherwise very limited. These two regions respond to growth factors and Neurog2 differently and instruct new neurons to exhibit distinct molecular phenotypes. Moreover, ischemic insult differentially affects differentiation of new neurons in these regions. These results demonstrate strong environmental impact on direct neuronal reprogramming in vivo.

Background: Patients with poor-grade aneurysmal subarachnoid hemorrhage (SAH) presenting with large intracerebral (ICH) or sylvian hematomas (SylH) have poor outcomes due to the mass effect of significant brain stem compression following mass effect. On the other hand, decompressive craniectomy (DC) can reduce morbidity and mortality in critically ill patients with massive ischemic infarction and severe head injury. However, the role of DC in SAH patients is not fully understood. We investigated the outcome of DC in poor-grade SAH presenting with large ICH or SylH. Methods: 110 consecutive patients with poor-grade SAH (Hunt & Kosnik (H&K) grades IV and V, and Fisher group 4) were admitted to our hospital between April 1, 1993, and July 30, 2004. We treated 57 of those who presented with large ICH or SylH using DC. We retrospectively reviewed medical charts, radiological findings, operative notes, and video records. Results: Among the 57 patients (mean age 57.8, male 29, female 28), 25 were classified as H&K grade IV and 32 as grade V. Ruptured aneurysms were located on the internal carotid artery in 11 and the middle cerebral artery in 46 patients. 50 of the aneurysms were small, 5 were medium, and 2 were large. Rerupture was preoperatively confirmed in 13 (22.8%). Hypothermia was applied to 17 (29.8%). The Glasgow Outcome Scale on discharge showed good recovery, moderate recovery, severe disability, vegetative state, and death in 8 (14.0%), 13 (22.8%), 16 (28.1%), 8 (14.0%), and 12 (21.1%), respectively. The outcomes of grade IV patients were favorable and poor in 14 (56.0%) and 10 (40.0%), respectively, and 1 (4.0%) died. Conclusion: Several experimental studies have also indicated that DC significantly improves outcome due to reduced intracranial pressure or increased perfusion pressure. Urgent DC for poor-grade SAH with space-occupying hematoma can lead to survival with good recovery in some patients.

Acute epidural hematomas (AEDH) are generally managed with rapid surgical hematoma evacuation and bleeding control. However, the surgical outcome of patients with serious brain edema is poor. This study reviewed the clinical outcome for AEDH patients and evaluated the efficacy of the DC, especially in patients with associated massive brain swelling. Eighty consecutive patients surgically treated with AEDH were retrospectively assessed. The patients were divided into two groups: (a) hematoma evacuation (HE: 46 cases) and (b) HE+ an external decompression (ED: 34 cases). The medical charts, operative findings, radiological findings, and operative notes were reviewed. In the poor outcome group, there were 18 patients (72%), with a GCS score of less than 8 (severe injury), and 22 patients (88%) who showed pupil abnormalities. Many more patients showed a midline shift, basal cistern effacement, and brain contusion in comparison to the favorable outcome group. In the favorable outcome group, almost all of the patients (98%) showed less than 12 mm of a midline shift. The influential factors may be age, GCS, pupil abnormalities, size, midline shift, basal cistern effacement, coincidence of contusion and swelling. We conclude that an A DC may be effective to manage the AEDH patients with cerebral contusion or massive brain swelling.

No abstract