Optogenetic Stimulation of Neural Grafts Enhances Neurotransmission and Downregulates the Inflammatory Response in Experimental Stroke Model.

Compelling evidence suggests that transplantation of neural stem cells (NSCs) from multiple sources ameliorates motor deficits after stroke. However, it is currently unknown to what extent the electrophysiological activity of grafted NSC progeny participates in the improvement of motor deficits and whether excitatory phenotypes of the grafted cells are beneficial or deleterious to sensorimotor performances. To address this question, we used optogenetic tools to drive the excitatory outputs of the grafted NSCs and assess the impact on local circuitry and sensorimotor performance. We genetically engineered NSCs to express the Channelrhodopsin-2 (ChR2), a light-gated cation channel that evokes neuronal depolarization and initiation of action potentials with precise temporal control to light stimulation. To test the function of these cells in a stroke model, rats were subjected to an ischemic stroke and grafted with ChR2-NSCs. The grafted NSCs identified with a human-specific nuclear marker survived in the peri-infarct tissue and coexpressed the ChR2 transgene with the neuronal markers TuJ1 and NeuN. Gene expression analysis in stimulated versus vehicle-treated animals showed a differential upregulation of transcripts involved in neurotransmission, neuronal differentiation, regeneration, axonal guidance, and synaptic plasticity. Interestingly, genes involved in the inflammatory response were significantly downregulated. Behavioral analysis demonstrated that chronic optogenetic stimulation of the ChR2-NSCs enhanced forelimb use on the stroke-affected side and motor activity in an open field test. Together these data suggest that excitatory stimulation of grafted NSCs elicits beneficial effects in experimental stroke model through cell replacement and non-cell replacement, anti-inflammatory/neurotrophic effects.

The contemporary management of renal artery aneurysms.

BACKGROUND: Renal artery aneurysms (RAAs) are rare, with little known about their natural history and growth rate or their optimal management. The specific objectives of this study were to (1) define the clinical features of RAAs, including the precise growth rate and risk of rupture, (2) examine the current management and outcomes of RAA treatment using existing guidelines, and (3) examine the appropriateness of current criteria for repair of asymptomatic RAAs. METHODS: A standardized, multi-institutional approach was used to evaluate patients with RAAs at institutions from all regions of the United States. Patient demographics, aneurysm characteristics, aneurysm imaging, conservative and operative management, postoperative complications, and follow-up data were collected. RESULTS: A total of 865 RAAs in 760 patients were identified at 16 institutions. Of these, 75% were asymptomatic; symptomatic patients had difficult-to-control hypertension (10%), flank pain (6%), hematuria (4%), and abdominal pain (2%). The RAAs had a mean maximum diameter of 1.5 ± 0.1 cm. Most were unilateral (96%), on the right side (61%), saccular (87%), and calcified (56%). Elective repair was performed in 213 patients with 241 RAAs, usually for symptoms or size >2 cm; the remaining 547 patients with 624 RAAs were observed. Major operative complications occurred in 10%, including multisystem organ failure, myocardial infarction, and renal failure requiring dialysis. RAA repair for difficult-to-control hypertension cured 32% of patients and improved it in 26%. Three patients had ruptured RAA; all were transferred from other hospitals and underwent emergency repair, with no deaths. Conservatively treated patients were monitored for a mean of 49 months, with no acute complications. Aneurysm growth rate was 0.086 cm/y, with no difference between calcified and noncalcified aneurysms. CONCLUSIONS: This large, contemporary, multi-institutional study demonstrated that asymptomatic RAAs rarely rupture (even when >2 cm), growth rate is 0.086 ± 0.08 cm/y, and calcification does not protect against enlargement. RAA open repair is associated with significant minor morbidity, but rarely a major morbidity or mortality. Aneurysm repair cured or improved hypertension in >50% of patients whose RAA was identified during the workup for difficult-to-control hypertension.

Current treatment of renal artery aneurysms may be too aggressive.

OBJECTIVE: Most studies recommend repair of renal artery aneurysms (RAAs) >2 cm in diameter in asymptomatic patients, but other studies have suggested that their natural history may be more benign. We hypothesized that rupture and death in patients with asymptomatic RAAs is low and that current recommendations for RAA treatment at 2 cm may be too aggressive. METHODS: Retrospective review of all RAAs treated at a tertiary care medical center from 2002 to 2012. RESULTS: Fifty-nine RAA were identified in 40 patients (mean age at diagnosis, 56 years; male:female ratio, 17:23); 31 were saccular, 8 were fusiform, and 5 were bilobed. Twenty-nine patients were asymptomatic; the remainder of patients presented with hematuria (n = 4), abdominal pain (n = 3), difficult-to-control hypertension (n = 3), or flank pain (n = 2). Aneurysm location included the main renal artery bifurcation (n = 35), main trunk (n = 7), primary branch (n = 6), pole artery (n = 6), and secondary branch (n = 1). Operative management of RAAs included vein patch (n = 6), prosthetic patch (n = 4), primary repair (n = 3), plication (n = 1), patch and implantation (n = 1), and ex vivo repair (n = 1). Eight asymptomatic RAAs were treated surgically (mean RAA diameter = 2.4 ± 0.1 cm, range, 2-3 cm), with the remaining 33 asymptomatic RAAs being managed conservatively (mean RAA diameter = 1.4 ± 0.1 cm, range, 0.6-2.6 cm). Mean hospital length of stay was 4 days, with no late postoperative complications and 0% mortality. Non-operated patients were followed for a mean of 36 ± 9 months, with no late acute complications and 0% mortality. Mean RAA growth rate of patients with multiple imaging studies was 0.60 ± 0.16 mm/y. CONCLUSIONS: The rate of aneurysm rupture and death in our untreated RAA patients is zero, the growth rate is 0.60 ± 0.16 mm/y, and there were no adverse outcomes in asymptomatic RAAs >2 cm that were observed. We may currently be too aggressive in treating asymptomatic RAAs.

Distal digital replantation.

BACKGROUND: Hand surgeons have been hesitant to perform distal digital replantation because of the technical challenges and the perception of a high cost-to-benefit ratio. Recent studies, however, have shown high survival rates and excellent functional and aesthetic results, providing renewed enthusiasm for distal replantation. METHODS: The authors reviewed the literature and summarize key points regarding the surgical treatment, perioperative care, and outcomes of distal digital replantation. They describe specific techniques and considerations for surgical repair in each of four distal zones as described by Sebastin and Chung. RESULTS: Zone 1A replantation involves an artery-only anastomosis of a longitudinal pulp artery. Venous anastomosis first becomes possible in zone 1B. Zone 1C involves periarticular amputations where arthrodesis of the distal interphalangeal joint is usually indicated. Repair of the artery, vein, and nerve is technically optimal in zone 1D, where venous anastomosis should be performed. Overall, survival rates for distal digital replantation are similar to those reported for more proximal replantation. The literature reports good outcomes regarding nail salvage, fingertip sensibility, and range of motion, with restoration of length and aesthetic appearance. CONCLUSIONS: Distal replantation performed at institutions that specialize in microsurgery and specifically tailored to the level of injury is associated with good survival, function, and patient satisfaction and superior aesthetic outcome. More prospective data are needed to evaluate the cost of treatment, psychological outcomes, and functional outcomes of distal replantation compared with revision amputation.

Female genomic response to mate information.

Females should be choosier than males about prospective mates because of the high costs of inappropriate mating decisions. Both theoretical and empirical studies have identified factors likely to influence female mate choices. However, male-male social interactions also can affect mating decisions, because information about a potential mate can trigger changes in female reproductive physiology. We asked how social information about a preferred male influenced neural activity in females, using immediate early gene (IEG) expression as a proxy for brain activity. A gravid female cichlid fish (Astatotilapia burtoni) chose between two socially equivalent males and then saw fights between these two males in which her preferred male either won or lost. We measured IEG expression levels in several brain nuclei including those in the vertebrate social behavior network (SBN), a collection of brain nuclei known to be important in social behavior. When the female saw her preferred male win a fight, SBN nuclei associated with reproduction were activated, but when she saw her preferred male lose a fight, the lateral septum, a nucleus associated with anxiety, was activated instead. Thus social information alone, independent of actual social interactions, activates specific brain regions that differ significantly depending on what the female sees. In female brains, reproductive centers are activated when she chooses a winner, and anxiety-like response centers are activated when she chooses a loser. These experiments assessing the role of mate-choice information on the brain using a paradigm of successive presentations of mate information suggest ways to understand the consequences of social information on animals using IEG expression.