Anatomic and Molecular Development of Corticostriatal Projection Neurons in Mice

Corticostriatal projection neurons (CStrPN) project from the neocortex to ipsilateral and contralateral striata to control and coordinate motor programs and movement. They are clinically important as the predominant cortical population that degenerates in Huntington's disease and corticobasal ganglionic degeneration, and their injury contributes to multiple forms of cerebral palsy. Together with their well-studied functions in motor control, these clinical connections make them a functionally, behaviorally, and clinically important population of neocortical neurons. Little is known about their development. “Intratelencephalic” CStrPN $(CStrPN_i)$, projecting to the contralateral striatum, with their axons fully within the telencephalon (intratelencephalic), are a major population of CStrPN. $CStrPN_i$ are of particular interest developmentally because they share hodological and axon guidance characteristics of both callosal projection neurons (CPN) and corticofugal projection neurons (CFuPN); $CStrPN_i$ send axons contralaterally before descending into the contralateral striatum. The relationship of $CStrPN_i$ development to that of broader CPN and CFuPN populations remains unclear; evidence suggests that $CStrPN_i$ might be evolutionary “hybrids” between CFuPN and deep layer CPN—in a sense “chimeric” with both callosal and corticofugal features. Here, we investigated the development of $CStrPN_i$ in mice—their birth, maturation, projections, and expression of molecular developmental controls over projection neuron subtype identity.Stem Cell and Regenerative Biolog

Role of Fever in Ventriculoperitoneal Shunt Placement After Aneurysmal Subarachnoid Hemorrhage

Abstract BACKGROUND: Central fever is common after aneurysmal subarachnoid hemorrhage (aSAH) and may delay ventriculoperitoneal shunt (VPS) placement. OBJECTIVE: We hypothesize that drain-dependent aSAH patients with central fever or persistent fever after treatment of an identifiable cause are not at an increased risk of infectious VPS failure. METHODS: Patient demographics, radiographic characteristics, temperature, incidence of infection, and shunt failure were prospectively recorded in a consecutive cohort of aSAH patients. Central fever was defined as temperature higher than 38.3°C with no identifiable cause. RESULTS: Of 580 patients, 61 (11%) were drain dependent. Central fever developed in 18, 35 had fever of known etiology, and 8 remained afebrile. There was no shunt failure at discharge, and 2 failures (3.2%) at follow-up were attributed to infection. One patient with central fever (6%), none with fever of identifiable etiology, and 1 (13%) with no fever had infectious shunt failures at a median follow-up of 10.2 ± 3.6 months (P > .05). Nine patients with central fever (50%) and 6 (17%) who were treated for fever of known etiologies had persistent fever at shunt placement. Patients who were febrile on the day of surgery had similar infectious shunt failure rates at discharge compared with those who were afebrile (0% vs 0%; P = 1.0). Similarly, febrile and afebrile patients at VPS insertion had comparable rates of infectious shunt failure at follow-up (7% vs 2%; P = .43). CONCLUSION: aSAH patients with central fever or persistent fever after treatment of fever of identifiable etiology are not at an increased risk of infectious VPS failure

Polymorphisms in complement component 3 (C3F) and complement factor H (Y402H) increase the risk of postoperative neurocognitive dysfunction following carotid endarterectomy

BACKGROUND: Up to 28% of patients undergoing carotid endarterectomy (CEA) are estimated to experience neurocognitive dysfunction following surgery. The complement cascade plays a central role in ischaemia-reperfusion injury. The authors investigated the effect of common polymorphisms in the complement component 3 (C3F) and complement factor H (CFH Y402H) genes on incidence of neurocognitive dysfunction post-CEA. METHODS: This study examined a nested cohort of prospectively recruited patients receiving elective CEA, who were genotyped for the C3F or Y402H polymorphisms. Each patient underwent a standard battery of eight neuropsychometric tests before, and 1 day and 30 days after, surgery. RESULTS: 57 of 142 (40%) CEA patients had at least one copy of the C3F allele (C3F+), and 17 of 137 (12%) patients had two copies of the CFH Y402H allele (Y402H++). At postoperative day 1, patients were three times (OR 3.05, p=0.045) or six times (OR 6.41, p=0.006) more likely to experience moderate-to-severe neurocognitive dysfunction if they carried the C3F+ or Y402H++ genotype, respectively. Patients with both risk genotypes had an almost eightfold risk of dysfunction (OR 7.67, p=0.046). Right-hand-dominant C3F+ subjects undergoing right-side CEA performed significantly worse on tests of visuospatial function than C3F- subjects. At day 30, C3F+ and Y402H++ genotypes trended towards significance as predictors of dysfunction (p=0.07 and p=0.22, respectively). CONCLUSION: The C3F and Y402H polymorphisms are strong independent predictors of moderate-to-severe neurocognitive dysfunction at 1 day following CEA. Furthermore, patients undergoing right-sided CEA are predisposed to deficits associated with cortex ipsilateral to the operative carotid artery

Gain-of-function polymorphisms of cystathionine β-synthase and delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage

OBJECT: Cystathionine β-synthase (CBS) is an enzyme that metabolizes homocysteine to form H(2)S in the brain. Hydrogen sulfide functions as a vasodilator as well as a regulator of neuronal ion channels and multiple intracellular signaling pathways. Given the myriad effects of H(2)S, the authors hypothesized that patients possessing gain-of-function polymorphisms of the CBS gene will experience a decreased incidence of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Patients were enrolled in a prospective observational database of aSAH outcomes. DNA was extracted from buccal swabs and sequenced for 3 functional polymorphisms of the CBS gene (699C→T, 844ins68, and 1080C→T) by polymerase chain reaction. Serum homocysteine levels (μmol/L) were assayed. Multivariate analysis was used to determine the relationship between CBS genotype and occurrence of both angiographic vasospasm and DCI. RESULTS: There were 87 patients included in the study. None of the polymorphisms investigated were significantly associated with the incidence of angiographic vasospasm. However, after controlling for admission hypertension, patients with the gain-of-function 844 WT/ins genotypes were less likely to experience DCI relative to those with the 844 WT/WT genotype (86 patients, p = 0.050), while the decrease-in-function genotype 1080 TT was more likely to experience DCI relative to those with 1080 CC and CT genotypes (84 patients, p = 0.042). Serum homocysteine levels did not correlate with the extent of either angiographic vasospasm or DCI in this analysis. CONCLUSIONS: Polymorphisms of the CBS gene that impart gain-of-function may be associated with a reduced risk of DCI after aSAH, independent of serum homocysteine. Signaling through H(2)S may mediate protection from DCI following aSAH through a mechanism that does not involve macrovascular vasodilation