Cocaine use is associated with cerebral white matter hyperintensities in HIV disease.

Background: White matter hyperintensities (WMH), a marker of cerebral small vessel disease and predictor of cognitive decline, are observed at higher rates in persons with HIV (PWH). The use of cocaine, a potent central nervous system stimulant, is disproportionately common in PWH and may contribute to WMH.

Methods: The sample included of 110 PWH on antiretroviral therapy.

Gold Nanostars Obviate Limitations to Laser Interstitial Thermal Therapy (LITT) for the Treatment of Intracranial Tumors.

Purpose: Laser interstitial thermal therapy (LITT) is an effective minimally invasive treatment option for intracranial tumors. Our group produced plasmonics-active gold nanostars (GNS) designed to preferentially accumulate within intracranial tumors and amplify the ablative capacity of LITT.

Experimental Design: The impact of GNS on LITT coverage capacity was tested in ex vivo models using clinical LITT equipment and agarose gel-based phantoms of control and GNS-infused central "tumors.

Durable responses in patients with HER2+ breast cancer and leptomeningeal metastases treated with trastuzumab deruxtecan.

Leptomeningeal metastases (LM) are a devastating complication of HER2 + metastatic breast cancer (MBC), with no effective treatments. In a case series of 8 patients with heavily pretreated HER2 + MBC and progressing LM, all 8 patients (100%) derived clinical benefit from Trastuzumab deruxtecan (TDXd), and 4 patients (50%) had an objective partial response based on formal neuroradiology MRI reads using the EORTC/RANO-LM Revised-Scorecard. T-DXd warrants further study in LM in HER2 + MBC and solid tumors where T-DXd may be active.

The Acute Effects of Time-Varying Caloric Vestibular Stimulation as Assessed With fMRI.

We describe preliminary results from the application of time-varying caloric vestibular stimulation (tvCVS) to volunteers during a continuous blood oxygen level dependent (BOLD) functional MRI (fMRI) acquisition, recording baseline, during-tvCVS and post-tvCVS epochs. The modifications necessary to enable the use of this novel device in a 3-Tesla magnetic field are discussed. Independent component analysis (ICA) was used as a model-free method to highlight spatially and temporally coherent brain networks.

CN-105 in Participants with Acute Supratentorial Intracerebral Hemorrhage (CATCH) Trial.

Background: Endogenous apolipoprotein (apo) E mediates neuroinflammatory responses and recovery after brain injury. Exogenously administered apoE-mimetic peptides effectively penetrate the central nervous system compartment and downregulate acute inflammation. CN-105 is a novel apoE-mimetic pentapeptide with excellent evidence of functional and histological improvement in preclinical models of intracerebral hemorrhage (ICH).

Neuroprotective Pentapeptide, CN-105, Improves Outcomes in Translational Models of Intracerebral Hemorrhage.

Background: Intracerebral hemorrhage (ICH) is a devastating form of cerebrovascular disease for which there are no approved pharmacological interventions that improve outcomes. Apolipoprotein E (apoE) has emerged as a promising therapeutic target given its isoform-specific neuroprotective properties and ability to modify neuroinflammatory responses. We developed a 5-amino acid peptide, CN-105, that mimics the polar face of the apoE helical domain involved in receptor interactions, readily crosses the blood-brain barrier, and improves outcomes in well-established preclinical ICH models.

Author Correction: Neuroprotective pentapeptide CN-105 improves functional and histological outcomes in a murine model of intracerebral hemorrhage.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Plasmonic gold nanostar-mediated photothermal immunotherapy for brain tumor ablation and immunologic memory.

Brain tumors present unique therapeutic challenges and they include glioblastoma (GBM) and metastases from cancers of other organs. Current treatment options are limited and include surgical resection, radiation therapy, laser interstitial thermal therapy and chemotherapy. Although much research has been done on the development of immune-based treatment platforms, only limited success has been demonstrated.

Annexin A1 Bioactive Peptide Promotes Resolution of Neuroinflammation in a Rat Model of Exsanguinating Cardiac Arrest Treated by Emergency Preservation and Resuscitation.

Neuroinflammation initiated by damage-associated molecular patterns, including high mobility group box 1 protein (HMGB1), has been implicated in adverse neurological outcomes following lethal hemorrhagic shock and polytrauma. Emergency preservation and resuscitation (EPR) is a novel method of resuscitation for victims of exsanguinating cardiac arrest, shown in preclinical studies to improve survival with acceptable neurological recovery. Sirtuin 3 (SIRT3), the primary mitochondrial deacetylase, has emerged as a key regulator of metabolic and energy stress response pathways in the brain and a pharmacological target to induce a neuronal pro-survival phenotype.

ABC Transporter Inhibition Plus Dexamethasone Enhances the Efficacy of Convection Enhanced Delivery in H3.3K27M Mutant Diffuse Intrinsic Pontine Glioma.

Background: An impermeable blood-brain barrier and drug efflux via ATP-binding cassette (ABC) transporters such as p-glycoprotein may contribute to underwhelming efficacy of peripherally delivered agents to treat diffuse intrinsic pontine glioma (DIPG).

Objective: To explore the pharmacological augmentation of convection-enhanced delivery (CED) infusate for DIPG.

Methods: The efficacy of CED dasatinib, a tyrosine kinase inhibitor, in a transgenic H3.

Sex Differences in Gene and Protein Expression After Intracerebral Hemorrhage in Mice.

Sex dimorphism has been demonstrated after experimental intracerebral hemorrhage (ICH). Decreased mortality and improved neurobehavioral outcomes occur in female compared to male mice after intrastriatal autologous blood or collagenase injection. Sex-specific differences in post-ICH gene and protein expression may provide mechanistic insight into this phenomenon.

BAG3 (Bcl-2-Associated Athanogene-3) Coding Variant in Mice Determines Susceptibility to Ischemic Limb Muscle Myopathy by Directing Autophagy.

Background: Critical limb ischemia is a manifestation of peripheral artery disease that carries significant mortality and morbidity risk in humans, although its genetic determinants remain largely unknown. We previously discovered 2 overlapping quantitative trait loci in mice, and , that affected limb muscle survival and stroke volume after femoral artery or middle cerebral artery ligation, respectively. Here, we report that a variant (Ile81Met) segregates with tissue protection from hind-limb ischemia.

The role of angiogenesis in Group 3 medulloblastoma pathogenesis and survival.

Background: Of the 4 medulloblastoma subgroups, Group 3 is the most aggressive but the importance of angiogenesis is unknown. This study sought to determine the role of angiogenesis and identify clinically relevant biomarkers of tumor vascularity and survival in Group 3 medulloblastoma.

Methods: VEGFA mRNA expression and survival from several patient cohorts were analyzed.

Neuroprotective pentapeptide CN-105 improves functional and histological outcomes in a murine model of intracerebral hemorrhage.

Presently, no pharmacological treatments have been demonstrated to improve long-term functional outcomes following intracerebral hemorrhage (ICH). Clinical evidence associates apolipoprotein E (apoE) genotype with ICH incidence and outcome. While apoE modifies neuroinflammatory responses through its adaptive role in glial downregulation, intact apoE holoprotein is too large to cross the blood-brain barrier (BBB).

Anticancer therapeutic potential of Mn porphyrin/ascorbate system.

Ascorbate (Asc) as a single agent suppressed growth of several tumor cell lines in a mouse model. It has been tested in a Phase I Clinical Trial on pancreatic cancer patients where it exhibited no toxicity to normal tissue yet was of only marginal efficacy. The mechanism of its anticancer effect was attributed to the production of tumoricidal hydrogen peroxide (H2O2) during ascorbate oxidation catalyzed by endogenous metalloproteins.

Sex-Specific Effects of Progesterone on Early Outcome of Intracerebral Hemorrhage.

Background: Preclinical evidence suggests that progesterone improves recovery after intracerebral hemorrhage (ICH); however, gonadal hormones have sex-specific effects. Therefore, an experimental model of ICH was used to assess recovery after progesterone administration in male and female rats.

Methods: ICH was induced in male and female Wistar rats via stereotactic intrastriatal injection of clostridial collagenase (0.

Modulation of murine breast tumor vascularity, hypoxia and chemotherapeutic response by exercise.

Exercise has been shown to improve postischemia perfusion of normal tissues; we investigated whether these effects extend to solid tumors. Estrogen receptor-negative (ER-, 4T1) and ER+ (E0771) tumor cells were implanted orthotopically into syngeneic mice (BALB/c, N = 11-12 per group) randomly assigned to exercise or sedentary control. Tumor growth, perfusion, hypoxia, and components of the angiogenic and apoptotic cascades were assessed by MRI, immunohistochemistry, western blotting, and quantitative polymerase chain reaction and analyzed with one-way and repeated measures analysis of variance and linear regression.

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 treatment and failure of large clinical trials aimed at hemostasis and clot removal demonstrate the need for further mechanism-driven investigation of ICH. This research may be performed through the framework provided by preclinical models.

Effects of deep hypothermic circulatory arrest on the blood brain barrier in a cardiopulmonary bypass model--a pilot study.

Background: 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).

Methods: Adult rats were subjected to CPB/DHCA or to sham surgery.

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

Background: 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.

Methods: Following induction of SAH, 12 ± 2 week old male C57-BL/6 mice received NP10075, a pH-dependent NMDA receptor antagonist, or vehicle.

ApolipoproteinE mimetic peptides improve outcome after focal ischemia.

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.

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

Background: 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.

Methods: Rats were subjected to 70 min temporary focal ischemia.