Suboccipital Cisterna Magna Injection for Vehicle Delivery in Pigs Using Computed Tomography.

Gene therapies are being developed for several central nervous system (CNS) disorders. These therapies are primarily administered to the CNS via the cerebrospinal fluid (CSF), as the blood-brain barrier prevents the transport of large molecules to the brain. Currently, intrathecal injection is the most commonly used route of administration over cisterna magna injections in the clinic for gaining access to the CSF.

Traumatic Brain Injury Alters the Trajectory of Age-Related Mitochondrial Change.

Background: Some epidemiologic studies associate traumatic brain injury (TBI) with Alzheimer's disease (AD).

Objective: To test whether a TBI-induced acceleration of age-related mitochondrial change could potentially mediate the reported TBI-AD association.

Methods: We administered unilateral controlled cortical impact (CCI) or sham injuries to 5-month-old C57BL/6J and tau transgenic rTg4510 mice.

An ASO therapy for Angelman syndrome that targets an evolutionarily conserved region at the start of the transcript.

Angelman syndrome is a devastating neurogenetic disorder for which there is currently no effective treatment. It is caused by mutations or epimutations affecting the expression or function of the maternally inherited allele of the ubiquitin-protein ligase E3A () gene. The paternal allele is imprinted in neurons of the central nervous system (CNS) by the antisense () transcript, which represents the distal end of the small nucleolar host gene 14 () transcription unit.

Unique Features of the Gut Microbiome Characterized in Animal Models of Angelman Syndrome.

A large subset of patients with Angelman syndrome (AS) suffer from concurrent gastrointestinal (GI) issues, including constipation, poor feeding, and reflux. AS is caused by the loss of ubiquitin ligase E3A () gene expression in the brain. Clinical features of AS, which include developmental delays, intellectual disability, microcephaly, and seizures, are primarily due to the deficient expression or function of the maternally inherited allele.

Comparing imaging biomarkers of cerebral edema after TBI in young adult male and female rats.

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Cerebral edema following TBI is known to play a critical role in injury severity and prognosis. In the current study we used multimodal magnetic resonance imaging (MRI) to assess cerebral edema 24 h after unilateral contusive TBI in male and female rats.

Immune response of human cultured cells towards macrocyclic FePO and FePC bioactive cyclophane complexes.

Synthetic molecules that mimic the function of natural enzymes or molecules have untapped potential for use in the next generation of drugs. Cyclic compounds that contain aromatic rings are macrocyclic cyclophanes, and when they coordinate iron ions are of particular interest due to their antioxidant and biomimetic properties. However, little is known about the molecular responses at the cellular level.

Evaluation of taurine neuroprotection in aged rats with traumatic brain injury.

Despite higher rates of hospitalization and mortality following traumatic brain injury (TBI) in patients over 65 years old, older patients remain underrepresented in drug development studies. Worse outcomes in older individuals compared to younger adults could be attributed to exacerbated injury mechanisms including oxidative stress, inflammation, blood-brain barrier disruption, and bioenergetic dysfunction. Accordingly, pleiotropic treatments are attractive candidates for neuroprotection.

Neuronal overexpression of Ube3a isoform 2 causes behavioral impairments and neuroanatomical pathology relevant to 15q11.2-q13.3 duplication syndrome.

Maternally derived copy number gains of human chromosome 15q11.2-q13.3 (Dup15q syndrome or Dup15q) cause intellectual disability, epilepsy, developmental delay, hypotonia, speech impairments, and minor dysmorphic features.

Genomic imprinting does not reduce the dosage of UBE3A in neurons.

Background: The ubiquitin protein E3A ligase gene () gene is imprinted with maternal-specific expression in neurons and biallelically expressed in all other cell types. Both loss-of-function and gain-of-function mutations affecting the dosage of UBE3A are associated with several neurodevelopmental syndromes and psychological conditions, suggesting that UBE3A is dosage-sensitive in the brain. The observation that loss of imprinting increases the dosage of UBE3A in brain further suggests that inactivation of the paternal allele evolved as a dosage-regulating mechanism.

14,15-Epoxyeicosa-5,8,11-trienoic Acid (14,15-EET) surrogates: carboxylate modifications.

The cytochrome P450 eicosanoid 14,15-epoxyeicosa-5,8,11-trienoic acid (14,15-EET) is a powerful endogenous autacoid that has been ascribed an impressive array of physiologic functions including regulation of blood pressure. Because 14,15-EET is chemically and metabolically labile, structurally related surrogates containing epoxide bioisosteres were introduced and have become useful in vitro pharmacologic tools but are not suitable for in vivo applications. A new generation of EET mimics incorporating modifications to the carboxylate were prepared and evaluated for vasorelaxation and inhibition of soluble epoxide hydrolase (sEH).

The effects of family therapies for adolescent delinquency and substance abuse: a meta-analysis.

This meta-analysis summarizes results from k = 24 studies comparing either Brief Strategic Family Therapy, Functional Family Therapy, Multidimensional Family Therapy, or Multisystemic Therapy to either treatment-as-usual, an alternative therapy, or a control group in the treatment of adolescent substance abuse and delinquency. Additionally, the authors reviewed and applied three advanced meta-analysis methods including influence analysis, multivariate meta-analysis, and publication bias analyses. The results suggested that as a group the four family therapies had statistically significant, but modest effects as compared to treatment-as-usual (d = 0.