Donald Seyfried

OBJECTIVE: Previous studies have demonstrated that transplanted multipotent mesenchymal stromal cells (MSCs) improve functional recovery in rats after experimental intracerebral hemorrhage (ICH). In this study the authors tested the hypothesis that administration of multipotent MSC-derived exosomes promotes functional recovery, neurovascular remodeling, and neurogenesis in a rat model of ICH. METHODS: Sixteen adult male Wistar rats were subjected to ICH via blood injection into the striatum, followed 24 hours later by tail vein injection of 100 μg protein of MSC-derived exosomes (treatment group, 8 rats) or an equal volume of vehicle (control group, 8 rats); an additional 8 rats that had identical surgery without blood infusion were used as a sham group. The modified Morris water maze (mMWM), modified Neurological Severity Score (mNSS), and social odor–based novelty recognition tests were performed to evaluate cognitive and sensorimotor functional recovery after ICH. All 24 animals were killed 28 days after ICH or sham procedure. Histopathological and immunohistochemical analyses were performed for measurements of lesion volume and neurovascular and white matter remodeling. RESULTS: Compared with the saline-treated controls, exosome-treated ICH rats showed significant improvement in the neurological function of spatial learning and motor recovery measured at 26–28 days by mMWM and starting at day 14 by mNSS (p < 0.05). Senorimotor functional improvement was measured by a social odor–based novelty recognition test (p < 0.05). Exosome treatment significantly increased newly generated endothelial cells in the hemorrhagic boundary zone, neuroblasts and mature neurons in the subventricular zone, and myelin in the striatum without altering the lesion volume. CONCLUSIONS: MSC-derived exosomes effectively improve functional recovery after ICH, possibly by promoting endogenous angiogenesis and neurogenesis in rats after ICH. Thus, cell-free, MSC-derived exosomes may be a novel therapy for ICH.

Postoperative urinary retention (POUR) is common in neurosurgical patients. The use of alpha-blockade therapy, such as tamsulosin, has benefited many patients with a history of obstructive uropathy by decreasing lower urinary tract symptoms such as distension, infections, and stricture formation, as well as the incidence of POUR. For this study, we targeted patients who had undergone spinal surgery to examine the prophylactic effects of tamsulosin. Increased understanding of this therapy will assist in minimizing the morbidity of spinal surgery. We enrolled 95 male patients undergoing spine surgery in a double-blind, randomized, placebo-controlled trial. Patients were randomly assigned to receive either preoperative tamsulosin (N = 49) or a placebo (N = 46) and then followed-up prospectively for the development of POUR after removal of an indwelling urinary catheter (IUC). They were also followed-up for the incidence of IUC reinsertions. The rate of developing POUR was similar in both the groups. Of the 49 patients given tamsulosin, 16 (36%) developed POUR compared to 13 (28%) from the control group (P = 0.455). In the control group, 5 (11%) patients had IUC re-inserted postoperatively, whereas 7 (14%) patients in the tamsulosin group had IUC re-inserted postoperatively (P = 0.616). In patients suffering from axial-type symptoms (i.e., mechanical back pain), 63% who received tamsulosin and 18% from the control group (P = 0.048) developed POUR. Overall, there was no statistically significant difference in the rates of developing POUR among patients in either group. POUR is caused by a variety of factors, and further studies are needed to shed light on its etiology.

Postoperative urinary retention (POUR) is a common problem in adult neurosurgical patients. The incidence of POUR is unknown and the etiology has not been well established. POUR can lead to urogenital damage, prolonged hospital stay, higher cost, and infection. This study elucidates several risk factors that contribute to POUR in a variety of neurosurgical patients in one institution. A total of 137 neurosurgical patients were prospectively followed up for the development of POUR, which we defined as initial postvoid residual (PVR1) >250 ml 6 hours after removal of an indwelling urinary catheter (IUC). For patients with PVR >250 ml on the third check, IUCs were reinserted and kept in for 5-7 days. Of the 137 patients, 68 (50%) were male, 41% (56/137) were 60 years or older, 86% (118/137) underwent spinal surgery, and 54% (74/137) had anesthesia over 200 minutes. Overall incidence of clinical POUR was 39.4% (54/137). Significantly higher rates of PVR1 >250 were noted in males, patients older than 60 years, and those who underwent spine surgery. When considering all patient characteristics (except selective alpha blockers), only gender, surgery time, and surgery type remained significant. In addition, PVR1 >250 was positively associated with longer length of stay. Of all patients, 24 (18%) had IUCs reinserted postoperatively or should have had one (5 refused and 2 had a third PVR). The association of IUC reinsertion with male gender was significant. Male gender, time of anesthesia >200 minutes, older age, and spinal surgery are the most significant risk factors associated with POUR in neurosurgical patients.