Peroxisome proliferator-activated receptor (PPAR)-γ is a ligand-activated transcription factor of nuclear hormone receptor superfamily. Thiazolidinedione rosiglitazone is a potent agonist of PPARγ which was shown to induce neuroprotection in animal models of focal ischemia and spinal cord injury. We currently evaluated the therapeutic potential of rosiglitazone (6 mg/kg at 5 min, 6 h and 24 h; i.p.) following controlled cortical impact (CCI)-induced traumatic brain injury (TBI) in adult mice. CCI injury increased the cortical PPARγ mRNA levels which were further elevated by rosiglitazone treatment. In addition, rosiglitazone treatment significantly decreased the cortical lesion volume measured at 7 days compared to vehicle treatment (by 56 ± 7%; p < 0.05; n = 6/group). Following TBI, the spared cortex of the rosiglitazone group showed significantly less numbers of GSI-B4+ activated microglia/macrophages and ICAM1+ capillaries, and curtailed induction of pro-inflammatory genes IL6, MCP1 and ICAM1 compared to vehicle group. Rosiglitazone-treated mice also showed significantly less number of TUNEL+ apoptotic neurons and curtailed induction of caspase-3 and Bax, compared to vehicle control. In addition, rosiglitazone significantly enhanced the post-TBI expression of the neuroprotective chaperones HSP27, HSP70 and HSP32/HO1, and the anti-oxidant enzymes catalase, Cu/Zn-SOD and Mn-SOD, compared to vehicle. Treatment with GW9662 (a specific PPARγ antagonist) prevented all the above PPARγ-mediated actions. Thus, PPARγ activation confers neuroprotection after TBI by anti-inflammatory, anti-apoptotic and anti-oxidative mechanisms.

Object There is little evidence addressing whether procedures requiring adjunctive devices lead to an increased frequency of thromboembolic complications. The authors report their experience with 155 aneurysms treated with and without adjunctive devices. Methods The authors retrospectively reviewed their last 155 aneurysm coil placement procedures. The patients' records were reviewed for the following phenomena: 1) evidence of procedure-related thrombus formation; 2) clinical evidence of stroke; and 3) the presence of acute ischemia in the treated vascular territory on diffusion-weighted (DW) imaging. Results Of the 155 aneurysms treated in 132 patients, 66 were treated with coils only, 45 had stent-assisted coil placement, 33 underwent balloon remodeling, and in 11 stents were placed after balloon remodeling. Small DW imaging abnormalities were present in the treated vascular territory in 24% of cases (37 lesions). Specifically, 21 (32%) of 66 lesions in the coil-treated group, 6 (13%) of 45 in the stent-assisted coil treatment group, 8 (24%) of 33 in the balloon remodeling group, and 2 (18%) of 11 in the balloon and stent group showed DW imaging positivity. Furthermore, 25 (68%) of the 37 cases that were positive on DW imaging occurred in patients presenting with subarachnoid hemorrhage (SAH). Clinically evident stroke or transient ischemic attack was present in 10 (27%) of 37 cases, with 70% occurring in patients presenting with SAH. Conclusions Use of adjunctive devices in treating aneurysms does not appear to increase the frequency of embolic or ischemic events. The presence of DW imaging abnormalities and clinically evident stroke was actually less frequent when adjunctive devices were used and in electively treated cases. This was probably related to perioperative antiplatelet medical management.

Early growth response‐1 (Egr1) is a sequence‐specific transcription factor (TF) which is induced under hypoxic conditions. We presently report that transient middle cerebral artery occlusion (MCAO) leads to increased expression of Egr1 in the brains of adult mice and rats between 2 h and 5 days of reperfusion with a peak increase of 8–12‐fold at 1 day. When subjected to transient MCAO and 3 days of reperfusion, Egr1−/− mice showed significantly smaller infarcts (by 44.9 ± 8.4%, p < 0.05) and improved neurological function than Egr1+/+ littermates. Following transient MCAO, brains of Egr1−/− mice showed less water accumulation and decreased neutrophil infiltration (by 42 ± 8%, p < 0.05) compared to Egr1+/+ mice. The number of activated microglia/macrophages were also significantly lower (OX42+ cells by 53 ± 9%, p < 0.05 and ED1+ cells by 59 ± 11%) in the post‐ischemic cortex of Egr1−/− mice compared to Egr1+/+ mice. In addition, post‐ischemic inflammatory gene expression was less pronounced in the brains of Egr1−/− mice compared to Egr1+/+ mice. Preventing cerebral Egr1 protein induction with small interference RNAs that target Egr1 decreased inflammatory gene expression and led to smaller infarcts (by 40.2 ± 6.9%, p < 0.05) and reduced neurological deficits in rats subjected to transient MCAO. Conversely, transient MCAO following adenoviral‐mediated Egr1 over‐expression exacerbated the infarct volume (by 29 ± 5.3%, p < 0.05) and worsened the neurological deficits in rats. These studies indicate Egr1 as a significant contributor of inflammation and neuronal damage after stroke.