scholarly journals Persistent Neurovascular Unit Dysfunction: Pathophysiological Substrate and Trigger for Late-Onset Neurodegeneration After Traumatic Brain Injury

2020 ◽  
Vol 14 ◽  
Author(s):  
Yunxiang Zhou ◽  
Qiang Chen ◽  
Yali Wang ◽  
Haijian Wu ◽  
Weilin Xu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Late Onset ◽  
Neurovascular Unit

scholarly journals Low-level blast exposure induces chronic vascular remodeling, perivascular astrocytic degeneration and vascular-associated neuroinflammation

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Miguel A. Gama Sosa ◽  
Rita De Gasperi ◽  
Dylan Pryor ◽  
Georgina S. Perez Garcia ◽  
Gissel M. Perez ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Vascular Remodeling ◽  
Late Onset ◽  
Neurovascular Unit ◽  
Microcomputed Tomography ◽  
Collagen Type Iv ◽  
Post Traumatic Stress ◽  
Type Iv ◽  
Cerebral Vascular

AbstractCerebral vascular injury as a consequence of blast-induced traumatic brain injury is primarily the result of blast wave-induced mechanical disruptions within the neurovascular unit. In rodent models of blast-induced traumatic brain injury, chronic vascular degenerative processes are associated with the development of an age-dependent post-traumatic stress disorder-like phenotype. To investigate the evolution of blast-induced chronic vascular degenerative changes, Long-Evans rats were blast-exposed (3 × 74.5 kPa) and their brains analyzed at different times post-exposure by X-ray microcomputed tomography, immunohistochemistry and electron microscopy. On microcomputed tomography scans, regional cerebral vascular attenuation or occlusion was observed as early as 48 h post-blast, and cerebral vascular disorganization was visible at 6 weeks and more accentuated at 13 months post-blast. Progression of the late-onset pathology was characterized by detachment of the endothelial and smooth muscle cellular elements from the neuropil due to degeneration and loss of arteriolar perivascular astrocytes. Development of this pathology was associated with vascular remodeling and neuroinflammation as increased levels of matrix metalloproteinases (MMP-2 and MMP-9), collagen type IV loss, and microglial activation were observed in the affected vasculature. Blast-induced chronic alterations within the neurovascular unit should affect cerebral blood circulation, glymphatic flow and intramural periarterial drainage, all of which may contribute to development of the blast-induced behavioral phenotype. Our results also identify astrocytic degeneration as a potential target for the development of therapies to treat blast-induced brain injury.

scholarly journals Prevalence of Traumatic Brain Injury in Early Versus Late-Onset Alzheimer’s Disease

2015 ◽  
Vol 47 (4) ◽  
pp. 985-993 ◽  
Author(s):  
Mario F. Mendez ◽  
Pongsatorn Paholpak ◽  
Andrew Lin ◽  
Jeannie Y. Zhang ◽  
Edmond Teng
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Late Onset

scholarly journals Annexin A2 Deficiency Exacerbates Neuroinflammation and Long-Term Neurological Deficits after Traumatic Brain Injury in Mice

2019 ◽  
Vol 20 (24) ◽  
pp. 6125 ◽  
Author(s):  
Ning Liu ◽  
Yinghua Jiang ◽  
Joon Yong Chung ◽  
Yadan Li ◽  
Zhanyang Yu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Neurovascular Unit ◽  
Annexin A2 ◽  
Tissue Loss ◽  
Neurological Deficits ◽  
Endogenous Factors ◽  
The Brain

Our laboratory and others previously showed that Annexin A2 knockout (A2KO) mice had impaired blood–brain barrier (BBB) development and elevated pro-inflammatory response in macrophages, implying that Annexin A2 (AnxA2) might be one of the key endogenous factors for maintaining homeostasis of the neurovascular unit in the brain. Traumatic brain injury (TBI) is an important cause of disability and mortality worldwide, and neurovascular inflammation plays an important role in the TBI pathophysiology. In the present study, we aimed to test the hypothesis that A2KO promotes pro-inflammatory response in the brain and worsens neurobehavioral outcomes after TBI. TBI was conducted by a controlled cortical impact (CCI) device in mice. Our experimental results showed AnxA2 expression was significantly up-regulated in response to TBI at day three post-TBI. We also found more production of pro-inflammatory cytokines in the A2KO mouse brain, while there was a significant increase of inflammatory adhesion molecules mRNA expression in isolated cerebral micro-vessels of A2KO mice compared with wild-type (WT) mice. Consistently, the A2KO mice brains had a significant increase in leukocyte brain infiltration at two days after TBI. Importantly, A2KO mice had significantly worse sensorimotor and cognitive function deficits up to 28 days after TBI and significantly larger brain tissue loss. Therefore, these results suggested that AnxA2 deficiency results in exacerbated early neurovascular pro-inflammation, which leads to a worse long-term neurologic outcome after TBI.

scholarly journals Associations Between Depression, Traumatic Brain Injury, and Cognitively-Defined Late-Onset Alzheimer’s Disease Subgroups

2019 ◽  
Vol 70 (2) ◽  
pp. 611-619 ◽  
Author(s):  
Julianna Bauman ◽  
Laura E. Gibbons ◽  
Mackenzie Moore ◽  
Shubhabrata Mukherjee ◽  
Susan M. McCurry ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Late Onset

scholarly journals PET-detectable tau pathology correlates with long-term neuropsychiatric outcomes in patients with traumatic brain injury

Brain ◽  
2019 ◽  
Vol 142 (10) ◽  
pp. 3265-3279 ◽  
Author(s):  
Keisuke Takahata ◽  
Yasuyuki Kimura ◽  
Naruhiko Sahara ◽  
Shunsuke Koga ◽  
Hitoshi Shimada ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Late Onset ◽  
Neuropsychiatric Symptoms ◽  
Tau Pathology ◽  
Long Term Outcomes

Is tau load associated with long-term outcomes of TBI? By using PET to assess tau deposits in patients with chronic TBI, Takahata et al. reveal elevated tau load compared to age-matched controls, and show that the abundance of tau in white matter is associated with late-onset neuropsychiatric symptoms.

scholarly journals Midline (central) fluid percussion model of traumatic brain injury in pediatric and adolescent rats

2018 ◽  
Vol 22 (1) ◽  
pp. 22-30 ◽  
Author(s):  
Rachel K. Rowe ◽  
Jordan L. Harrison ◽  
Timothy W. Ellis ◽  
P. David Adelson ◽  
Jonathan Lifshitz
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Late Onset ◽  
Human Condition ◽  
Acute Injury ◽  
Behavioral Deficits ◽  
Fluid Percussion ◽  
Skull Size ◽  
Righting Reflex ◽  
Old Rats

OBJECTIVEExperimental traumatic brain injury (TBI) models hold significant validity to the human condition, with each model replicating a subset of clinical features and symptoms. TBI is the leading cause of mortality and morbidity in children and teenagers; thus, it is critical to develop preclinical models of these ages to test emerging treatments. Midline fluid percussion injury (FPI) might best represent mild and diffuse clinical brain injury because of the acute behavioral deficits, the late onset of behavioral morbidities, and the absence of gross histopathology. In this study, the authors sought to adapt a midline FPI to postnatal day (PND) 17 and 35 rats. The authors hypothesized that scaling the craniectomy size based on skull dimensions would result in a reproducible injury comparable to the standard midline FPI in adult rats.METHODSPND17 and PND35 rat skulls were measured, and trephines were scaled based on skull size. Custom trephines were made. Rats arrived on PND10 and were randomly assigned to one of 3 cohorts: PND17, PND35, and 2 months old. Rats were subjected to midline FPI, and the acute injury was characterized. The right reflex was recorded, injury-induced apnea was measured, injury-induced seizure was noted, and the brains were immediately examined for hematoma.RESULTSThe authors’ hypothesis was supported; scaling the trephines based on skull size led to a reproducible injury in the PND17 and PND35 rats that was comparable to the injury in a standard 2-month-old adult rat. The midline FPI suppressed the righting reflex in both the PND17 and PND35 rats. The injury induced apnea in PND17 rats that lasted significantly longer than that in PND35 and 2-month-old rats. The injury also induced seizures in 73% of PND17 rats compared with 9% of PND35 rats and 0% of 2-month-old rats. There was also a significant relationship between the righting reflex time and presence of seizure. Both PND17 and PND35 rats had visible hematomas with an intact dura, indicative of diffuse injury comparable to the injury observed in 2-month-old rats.CONCLUSIONSWith these procedures, it becomes possible to generate brain-injured juvenile rats (pediatric [PND17] and adolescent [PND35]) for studies of injury-induced pathophysiology and behavioral deficits, for which rational therapeutic interventions can be implemented.

scholarly journals Temporal Profile of Transporter mRNA Expression in the Brain after Traumatic Brain Injury in Developing Rats

2019 ◽  
Author(s):  
Solomon M. Adams ◽  
Fanuel T. Hagos ◽  
Jeffrey P. Cheng ◽  
Robert S. B. Clark ◽  
Patrick M. Kochanek ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mrna Expression ◽  
Neurovascular Unit ◽  
Post Injury ◽  
Adult Rats ◽  
Order Of Magnitude ◽  
Liver And Kidney ◽  
The Central Nervous System ◽  
The Brain

ABSTRACTTraumatic brain injury (TBI) is a leading cause of death in children and young adults; however, new pharmacologic approaches have failed to improve outcomes in clinical trials. Transporter proteins are central to the maintenance of homeostasis within the neurovascular unit, and regulate drug penetration into the brain. Our objective was to measure transporter temporal changes in expression in the hippocampus and cortex after experimental TBI in developing rats. We also evaluated the expression of transporters in brain, liver, and kidney across the age spectrum in both pediatric and adult rats. Eighty post-natal day (PND)-17 rats and four adult rats were randomized to receive controlled cortical impact (CCI), sham surgery, or no surgery. mRNA transcript counts for 27 ATP-binding cassette and solute carrier transporters were measured in the hippocampus, cortex, choroid plexus, liver, and kidney at 3h, 12h, 24h, 72h, 7d, and 14d post injury. After TBI, the expression of many transporters (Abcc2, Slc15a2, Slco1a2) decreased significantly in the first 24 hours, with a return to baseline over 7-14 days. Some transporters (Abcc4, Abab1a/b, Slc22a4) showed a delayed increase in expression. Baseline expression of transporters was of a similar order of magnitude in brain tissues relative to liver and kidney. Findings suggest that transporter-regulated processes may be impaired in the brain early after TBI and are potentially involved in the recovery of the neurovascular unit. Our data also suggest that transport-dependent processes in the brain are of similar importance as those seen in organs involved in drug metabolism and excretion.Significance StatementBaseline transporter mRNA expression in the central nervous system is of similar magnitude as liver and kidney, and experimental traumatic brain injury is associated with acute decrease in expression of several transporters, while others show delayed increase or decrease in expression. Pharmacotherapy following traumatic brain injury should consider potential pharmacokinetic changes associated with transporter expression.

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