Evidence of early vasogenic edema following minor head impact that can be reduced with a vasopressin V1a receptor antagonist

Kulkarni, Praveen; Bhosle, Mansi R.; Lu, Shi-fang; Simon, Neal; Iriah, Sade; Brownstein, Michael J.; Ferris, Craig F.

doi:10.1016/j.brainresbull.2020.10.001

Cited by 14 publications

(12 citation statements)

References 69 publications

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“…At the present time we can provide no satisfying answers to any of these questions. The inverse relationship between these measures of anisotropy is not unexpected and typical in studies of brain injury where vasogenic edema, caused by an increase in blood brain permeability, expands the extracellular space increasing ADC while reducing FA 42 . Conversely, cytotoxic edema characterised by cellular swelling and expansion of the intracellular space decreases ADC and increases FA 43 .…”

Section: Discussionmentioning

confidence: 75%

“…This study exposed female and male mice to vaporised cannabis containing 10.3% THC for 28 days starting at PND 23 and ending at PND 51. This period of periadolescence has been divided into early prepubescence (PND 22-34), midpubescence (PND [35][36][37][38][39][40][41][42][43][44][45][46][47] and late adolescence with sexually maturity (PND 48-60). 58 It is estimated that during this periadolescent period, 3.65 mouse days is equal to one human year 59 a treatment period that would equate to approximately 7.7 years in humans.…”

Section: Limitations and Data Interpretationmentioning

confidence: 99%

“…The inverse relationship between these measures of anisotropy is not unexpected and typical in studies of brain injury where vasogenic edema, caused by an increase in blood brain permeability, expands the extracellular space increasing ADC while reducing FA. 42 Conversely, cytotoxic edema characterised by cellular swelling and expansion of the intracellular space decreases ADC and increases FA. 43 It is unlikely that this pattern of water diffusivity is due to gross injury to the forebrain and hindbrain in females exposed to cannabis during periadolescence.…”

Section: Dwimentioning

confidence: 99%

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Changes in brain structure and function following chronic exposure to inhaled vaporised cannabis during periadolescence in female and male mice: A multimodal MRI study

et al. 2022

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Background and Aims Social norms and legality surrounding the use of medical and recreational cannabis are changing rapidly. The prevalence of cannabis use in adolescence is increasing. The aim of this study was to assess any sex‐based neurobiological effects of chronically inhaled, vaporised cannabis on adolescent female and male mice. Methods Female and male mice were exposed daily to vaporised cannabis (10.3% Δ‐9‐tetrahydrocannabinol [THC] and 0.05% cannabidiol [CBD]) or placebo from postnatal day 23 to day 51. Following cessation of treatment, mice were examined for changes in brain structure and function using noninvasive multimodal magnetic resonance imaging (MRI). Data from voxel‐based morphometry, diffusion weighted imaging and rest state functional connectivity were registered to and analysed with a 3D mouse atlas with 139 brain areas. Following imaging, mice were tested for their preference for a novel object. Results The effects were sexually dimorphic with females showing a unique distribution and inverse correlation between measures of fractional anisotropy and apparent diffusion coefficient localised to the forebrain and hindbrain. In contrast males displayed significant increased functional coupling with the thalamus, hypothalamus and brainstem reticular activating system as compared with controls. Cannabis males also presented with altered hippocampal coupling and deficits in cognitive function. Conclusion Chronic exposure to inhaled vaporised cannabis had significant effects on brain structure and function in early adulthood corroborating much of the literature. Females presented with changes in grey matter microarchitecture, while males showed altered functional connectivity in hippocampal circuitry and deficits in object recognition.

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Section: Discussionmentioning

confidence: 75%

Section: Limitations and Data Interpretationmentioning

confidence: 99%

Section: Dwimentioning

confidence: 99%

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Changes in brain structure and function following chronic exposure to inhaled vaporised cannabis during periadolescence in female and male mice: A multimodal MRI study

et al. 2022

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“…Histological validation of changes in BBB permeability is a snapshot of a single time point of a dynamic process that is biphasic as described by Logsdon et al ( 21 ), with an onset and duration noted by Tagge et al ( 22 ). In a just published study using apparent diffusion coefficient from diffusion weighted imaging as a proxy of vasogenic edema from disruption in BBB permeability, we reported increased edema that peaked at 6 h post one mild head impact that resolved within 24 h ( 58 ). Hence post-mortem histology for assessing BBB permeability has its limitations set by the time from insult to animal sacrifice.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Imaging of Blood-Brain Barrier Permeability Following Repetitive Mild Head Impacts

Leaston¹,

Qiao

Harding

et al. 2021

Front. Neurol.

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This was an exploratory study designed to evaluate the feasibility of a recently established imaging modality, quantitative ultrashort time-to-echo contrast enhanced (QUTE-CE), to follow the early pathology and vulnerability of the blood brain barrier in response to single and repetitive mild head impacts. A closed-head, momentum exchange model was used to produce three consecutive mild head impacts aimed at the forebrain separated by 24 h each. Animals were measured at baseline and within 1 h of impact. Anatomical images were collected to assess the extent of structural damage. QUTE-CE biomarkers for BBB permeability were calculated on 420,000 voxels in the brain and were registered to a bilateral 3D brain atlas providing site-specific information on 118 anatomical regions. Blood brain barrier permeability was confirmed by extravasation of labeled dextran. All head impacts occurred in the absence of any structural brain damage. A single mild head impact had measurable effects on blood brain barrier permeability and was more significant after the second and third impacts. Affected regions included the prefrontal ctx, basal ganglia, hippocampus, amygdala, and brainstem. Our findings support the concerns raised by the healthcare community regarding mild head injuries in participants in organized contact sports and military personnel in basic training and combat.

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“…27 , 28 The kinetic energy at impact was 1.37 joules. 29 We have used this model to publish on the neuroradiological effects of a single mild head impact, 30 multiple mild impacts 31 and moderate brain injury in rats. 32 The impact piston was directed to the top of the skull, midline, in the approximate area of Bregma (see Supplementary Fig.…”

Section: Methodsmentioning

confidence: 99%

Mild repetitive head impacts alter perivascular flow in the midbrain dopaminergic system in awake rats

Cai

Harding

Sadaka

et al. 2021

Brain Communications

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Head injury is a known risk factor for Parkinson’s disease. Disruption in the perivascular clearance of metabolic waste and unwanted proteins is thought to be a contributing factor to disease progression. We hypothesized that repetitive mild head impacts, without evidence of structural brain damage, would increase microgliosis and AQP4 expression and depolarization and alter perivascular flow in the midbrain dopaminergic system. Adult male rats were subjected to sham, or two mild head impacts separated by 48 h. Three weeks later, fully awake rats were imaged using dynamic, contrast-enhanced MRI to follow the distribution of intraventricular gadobenate dimeglumine contrast agent. Images were registered to and analysed using a 3D MRI rat atlas providing site-specific data on 171 different brain areas. Following imaging, rats were tested for cognitive function using the Barnes maze assay. Histological analyses of tyrosine hydroxylase, microglia activation and AQP4 expression and polarization were performed on a parallel cohort of head impacted rats at 20 days post insult to coordinate with the time of imaging. There was no change in the global flux of contrast agent between sham and head impacted rats. The midbrain dopaminergic system showed a significant decrease in the influx of contrast agent as compared to sham controls together with a significant increase in microgliosis, AQP4 expression and depolarization. There were no deficits in cognitive function. The histology showed a significant level of neuroinflammation in the midbrain dopaminergic system 3 weeks post mild repetitive head impact but no loss in tyrosine hydroxylase. MRI revealed no structural brain damage emphasizing the potential serious consequences of mild head impacts on sustained brain neuroinflammation in this area critical to the pathophysiology of Parkinson’s.

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Evidence of early vasogenic edema following minor head impact that can be reduced with a vasopressin V1a receptor antagonist

Cited by 14 publications

References 69 publications

Changes in brain structure and function following chronic exposure to inhaled vaporised cannabis during periadolescence in female and male mice: A multimodal MRI study

Changes in brain structure and function following chronic exposure to inhaled vaporised cannabis during periadolescence in female and male mice: A multimodal MRI study

Quantitative Imaging of Blood-Brain Barrier Permeability Following Repetitive Mild Head Impacts

Mild repetitive head impacts alter perivascular flow in the midbrain dopaminergic system in awake rats

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