intrastriatal-injection-autologous-blood-or-clostridial-collagenase

Intrastriatal Injection of Autologous Blood or Clostridial Collagenase as Murine Models of Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is a common form of cerebrovascular disease and is associated with significant morbidity and mortality. Lack of effective ...

Duke University

Gliosis refers to a range of glial cell transformations that vary according to specific brain pathologic states. Disease, however, is not a prerequisite for gliosis because glial reactivity may also be seen in regions of increased physiologic activity. Our study tests the hypothesis that high-field-strength magnetization transfer MRI is a sensitive technique for detecting transient glial reactivity after experimental spreading depression, a relatively benign perturbation unaccompanied by cell injury.

Changes in magnetization transfer MRI correlate with spreading depression-induced astroglial reactivity and increased protein expression in mice.

Diffusion tensor tractography: exploring the cost-benefit ratio of incorporating CSF suppression into fiber tracing algorithms.

The purpose of the study was to evaluate the effect of APOE genotype and the feasibility of administering an apolipoprotein E-mimetic therapeutic to modify outcomes in a murine model of intracerebral hemorrhage.

Pharmacogenomic effects of apolipoprotein e on intracerebral hemorrhage.

There is emerging evidence to suggest that brain natriuretic peptide (BNP) is elevated after acute brain injury, and that it may play an adaptive role in recovery through augmentation of cerebral blood flow (CBF). Through a series of experiments, we tested the hypothesis that the administration of BNP after different acute mechanisms of central nervous system (CNS) injury could improve functional recovery by improving CBF. C57 wild-type mice were exposed to either pneumatic-induced closed traumatic brain injury (TBI) or collagenase-induced intracerebral hemorrhage (ICH). After injury, either nesiritide (hBNP) (8 microg/kg) or normal saline were administered via tail vein injection at 30 min and 4 h. The mice then underwent functional neurological testing via rotorod latency over the following 5 days and neurocognitive testing via Morris water maze testing on days 24-28. Cerebral blood flow (CBF) was assessed by laser Doppler from 25 to 90 min after injury. After ICH, mRNA polymerase chain reaction (PCR) and histochemical staining were performed during the acute injury phase (<24 h) to determine the effects on inflammation. Following TBI and ICH, administration of hBNP was associated with improved functional performance as assessed by rotorod and Morris water maze latencies (p < 0.01). CBF was increased (p < 0.05), and inflammatory markers (TNF-alpha and IL-6; p < 0.05), activated microglial (F4/80; p < 0.05), and neuronal degeneration (Fluoro-Jade B; p < 0.05) were reduced in mice receiving hBNP. hBNP improves neurological function in murine models of TBI and ICH, and was associated with enhanced CBF and downregulation of neuroinflammatory responses. hBNP may represent a novel therapeutic strategy after acute CNS injury.

Brain natriuretic peptide improves long-term functional recovery after acute CNS injury in mice.

CT fluoroscopy-assisted cervical transforaminal steroid injection is an effective therapeutic option for cervical radiculopathy, yet it is approached with trepidation by some interventionalists. CT fluoroscopy is superior to conventional fluoroscopy for delineating complex anatomic relations in the neck but must be combined with careful technique to avoid rare but serious complications. We describe the anatomy of the neural foramen, our technique of CT fluoroscopy-assisted cervical transforaminal steroid injection, and the CT appearance of appropriate and inappropriate needle positions.

CT fluoroscopy-assisted cervical transforaminal steroid injection: tips, traps, and use of contrast material.

Autism spectrum disorders (ASDs) comprise a range of disorders that share a core of neurobehavioural deficits characterized by widespread abnormalities in social interactions, deficits in communication as well as restricted interests and repetitive behaviours. The neurological basis and circuitry mechanisms underlying these abnormal behaviours are poorly understood. SHANK3 is a postsynaptic protein, whose disruption at the genetic level is thought to be responsible for the development of 22q13 deletion syndrome (Phelan-McDermid syndrome) and other non-syndromic ASDs. Here we show that mice with Shank3 gene deletions exhibit self-injurious repetitive grooming and deficits in social interaction. Cellular, electrophysiological and biochemical analyses uncovered defects at striatal synapses and cortico-striatal circuits in Shank3 mutant mice. Our findings demonstrate a critical role for SHANK3 in the normal development of neuronal connectivity and establish causality between a disruption in the Shank3 gene and the genesis of autistic-like behaviours in mice.

Shank3 mutant mice display autistic-like behaviours and striatal dysfunction.

The purpose of this article is to compare the radiation dose of conventional fluoroscopy-guided lumbar epidural steroid injections (ESIs) and CT fluoroscopy (CTF)-guided lumbar ESI using both clinical data and anthropomorphic phantoms.

Radiation dose exposure for lumbar spine epidural steroid injections: a comparison of conventional fluoroscopy data and CT fluoroscopy techniques.

The purpose of this study is to investigate the effects of exercise on cancer progression, metastasis, and underlying mechanisms in an orthotopic model of murine prostate cancer. C57BL/6 male mice (6-8 wk of age) were orthotopically injected with transgenic adenocarcinoma of mouse prostate C-1 cells (5 × 10(5)) and randomly assigned to exercise (n = 28) or a non-intervention control (n = 31) groups. The exercise group was given voluntary access to a wheel 24 h/day for the duration of the study. Four mice per group were serially killed on days 14, 31, and 36; the remaining 38 mice (exercise, n = 18; control, n = 20) were killed on day 53. Before death, MRI was performed to assess tumor blood perfusion. Primary tumor growth rate was comparable between groups, but expression of prometastatic genes was significantly modulated in exercising animals with a shift toward reduced metastasis. Exercise was associated with increased activity of protein kinases within the MEK/MAPK and PI3K/mTOR signaling cascades with subsequent increased intratumoral protein levels of HIF-1α and VEGF. This was associated with improved tumor vascularization. Multiplex ELISAs revealed distinct reductions in plasma concentrations of several angiogenic cytokines in the exercise group, which was associated with increased expression of angiogenic and metabolic genes in the skeletal muscle. Exercise-induced stabilization of HIF-1α and subsequent upregulation of VEGF was associated with "productive" tumor vascularization with a shift toward suppressed metastasis in an orthotopic model of prostate cancer.

Exercise modulation of the host-tumor interaction in an orthotopic model of murine prostate cancer.

Xenon has been proven to be neuroprotective in experimental brain injury. The authors hypothesized that xenon would improve outcome from focal cerebral ischemia with a delayed treatment onset and prolonged recovery interval.

Xenon neuroprotection in experimental stroke: interactions with hypothermia and intracerebral hemorrhage.

Growing clinical evidence implicates isoform-specific effects of apolipoprotein E (apoE) in reducing neuroinflammation and mediating adaptive responses following ischemic and traumatic brain injury. However, the intact apoE holoprotein does not cross the blood-brain barrier and thus has limited therapeutic potential. We have created a small peptide, COG1410 (acetyl-AS-Aib-LRKL-Aib-KRLL-amide), derived from the apoE receptor-binding region. COG1410 retains the anti-inflammatory and neuroprotective biological properties of the intact holoprotein and penetrates the blood-brain barrier. In the current study, we utilized a murine model of transient focal cerebral ischemia and reperfusion to demonstrate that intravenous (IV) administration of COG1410 reduces infarct volume and radiographic progression of infarct, and improves functional outcome as assessed by rotarod when delivered up to 4h after ischemia onset.

ApolipoproteinE mimetic peptides improve outcome after focal ischemia.

Despite intensive research, neurological morbidity from delayed cerebral ischemia remains common after aneurysmal subarachnoid hemorrhage (SAH). In the current study, we evaluate the neuroprotective effects of a pH-dependent GluN2B subunit-selective NMDA receptor antagonist in a murine model of SAH.

pH-sensitive NMDA inhibitors improve outcome in a murine model of SAH.

Neurologic injury is common after cardiac surgery and disruption of the blood brain barrier (BBB) has been proposed as a contributing factor. We sought to study BBB characteristics in a rodent model of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA).

Article	Year
Changes in magnetization transfer MRI correlate with spreading depression-induced astroglial reactivity and increased protein expression in mice. AJR. American journal of roentgenology\| PubMed ID: 15547231	2004
Diffusion tensor tractography: exploring the cost-benefit ratio of incorporating CSF suppression into fiber tracing algorithms. AJNR. American journal of neuroradiology\| PubMed ID: 15814906	2005
Pharmacogenomic effects of apolipoprotein e on intracerebral hemorrhage. Stroke; a journal of cerebral circulation\| PubMed ID: 19109539	2009
Brain natriuretic peptide improves long-term functional recovery after acute CNS injury in mice. Journal of neurotrauma\| PubMed ID: 19803787	2010
CT fluoroscopy-assisted cervical transforaminal steroid injection: tips, traps, and use of contrast material. AJR. American journal of roentgenology\| PubMed ID: 20858814	2010
Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature\| PubMed ID: 21423165	2011
Radiation dose exposure for lumbar spine epidural steroid injections: a comparison of conventional fluoroscopy data and CT fluoroscopy techniques. AJR. American journal of roentgenology\| PubMed ID: 21940563	2011
Exercise modulation of the host-tumor interaction in an orthotopic model of murine prostate cancer. Journal of applied physiology (Bethesda, Md. : 1985)\| PubMed ID: 22604887	2012
Xenon neuroprotection in experimental stroke: interactions with hypothermia and intracerebral hemorrhage. Anesthesiology\| PubMed ID: 23143806	2012
ApolipoproteinE mimetic peptides improve outcome after focal ischemia. Experimental neurology\| PubMed ID: 23219883	2013
pH-sensitive NMDA inhibitors improve outcome in a murine model of SAH. Neurocritical care\| PubMed ID: 24420693	2014
Effects of Deep Hypothermic Circulatory Arrest on the Blood Brain Barrier in a Cardiopulmonary Bypass Model - A Pilot Study. Heart, lung & circulation\| PubMed ID: 24931068	2014

Christopher D. Lascola

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