Sex-specific pathological response to Traumatic Brain Injury
(2022) MOBN03 20212Degree Projects in Molecular Biology
- Abstract
- Traumatic brain injury (TBI) is one of leading causes of death in the world; survivors commonly exhibit behavioural changes and neurocognitive defects in the long-term. Following TBI, rapid changes in the neurovascular unit (NVU) occur as the permeability of the blood brain barrier (BBB) increases and cerebral blood flow (CBF) becomes dysregulated. An integral component of the NVU are pericytes which help maintain the integrity of the BBB, which are lost following mTBI resulting in BBB permeability and consequential leakage of blood plasma proteins into the brain parenchyma. After sustaining a TBI, females are more likely to develop persistent symptoms and show greater cognitive impairment than males. Importantly, the underlying causes for... (More)
- Traumatic brain injury (TBI) is one of leading causes of death in the world; survivors commonly exhibit behavioural changes and neurocognitive defects in the long-term. Following TBI, rapid changes in the neurovascular unit (NVU) occur as the permeability of the blood brain barrier (BBB) increases and cerebral blood flow (CBF) becomes dysregulated. An integral component of the NVU are pericytes which help maintain the integrity of the BBB, which are lost following mTBI resulting in BBB permeability and consequential leakage of blood plasma proteins into the brain parenchyma. After sustaining a TBI, females are more likely to develop persistent symptoms and show greater cognitive impairment than males. Importantly, the underlying causes for the differences in recovery following TBI are not well understood. Here, we investigate sex-specific differences following experimental TBI, by targeting capillary CD31 and Podocalyxin and pericyte PDGFrβ in the lateral cortex of mice with immunohistochemical and immunofluorescent techniques. Using an in vivo central fluid percussion injury (cFPI) model, male and female mice were analysed at day 2, 7 and 30 post-injury and were compared with controls. Our findings show that male capillaries and pericytes do not change following cFPI, whereas females showed a response in both capillaries and pericytes. Female mice exhibited reduced capillary width 30 days after cFPI as well as early phase response in pericytes. Our data suggests that sex-specific differences occur in capillaries and in pericytes following cFPI. Further research is required to determine the underlying mechanisms driving sex-specific responses, which may potentially lead to the development of sex-specific therapeutic interventions for TBI. (Less)
- Popular Abstract
- Sex-specific pathological response to Traumatic Brain Injury
Traumatic brain injury (TBI) is one of the leading causes of death in the world. Harsh insults to the head can have long lasting impacts on physical and mental health. TBI isn’t solely a physical injury; intricate mechanisms at the molecular level are triggered potentially causing further harm which only become visible much later in life. Currently TBI is being more frequently linked to a class of neurodegenerative diseases which include Alzheimer’s and Dementia.
The blood vessel network in the brain is a highly complex interplay of different cell types to make up the blood brain barrier (BBB). One of the cell types that are critical to the BBB are pericytes. Pericytes... (More) - Sex-specific pathological response to Traumatic Brain Injury
Traumatic brain injury (TBI) is one of the leading causes of death in the world. Harsh insults to the head can have long lasting impacts on physical and mental health. TBI isn’t solely a physical injury; intricate mechanisms at the molecular level are triggered potentially causing further harm which only become visible much later in life. Currently TBI is being more frequently linked to a class of neurodegenerative diseases which include Alzheimer’s and Dementia.
The blood vessel network in the brain is a highly complex interplay of different cell types to make up the blood brain barrier (BBB). One of the cell types that are critical to the BBB are pericytes. Pericytes directly interact with the blood vessels in the brain and are critical for maintaining the BBB and cerebral blood flow (CBF). In the early stage of TBI, the density of the blood vessel network is decreased and pericyte interaction with the blood vessel network is reduced, leading to BBB leakage into the brain and loss of CBF control.
Recently, research has focused on whether sex-differences exist in TBI. Findings suggest that differences in response to TBI and recovery between the sexes do exist. However, it is not well known why such disparities occur. Therefore, determining the mechanisms driving sex-specific differences in TBI is critical to improve clinical prognosis and patient outcome. We hypothesised that the sex specific differences in TBI exist at the BBB level. Therefore, in our study, we investigated the sex-specific responses of blood vessels and pericytes using a mild TBI mouse model.
Using microscopy techniques, we imaged the blood vessels and pericytes of male and female mice 2, 7 and 30 days after TBI. We found that females exhibited a response in both the blood vessels and pericytes. In female mice, the diameter of blood vessels was found to be significantly decreased at 30 days, whilst the number of vessel branches increased one week after injury. Pericytes in female mice were found to exhibit increased capillary coverage in the early stages of mild TBI, which then returned to a normal state. Unlike in female mice, males did not show a response in blood vessels or pericytes following mild TBI over 30 days.
Our findings support that sex-specific differences exist following mTBI and differential responses occur in blood vessels as well as pericytes. Further research is required to determine which mechanisms at the molecular level are driving such differences.
Master’s Degree Project Molecular Biology 60 credits 2021-2022 Department of Biology, Lund University
Advisor: Advisors: Prof. Niklas Marklund, Ilknur Özen
Lund Brain Injury laboratory for Neurosurgical research (LUBIN) (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9103264
- author
- Fry, Christopher
- supervisor
- organization
- course
- MOBN03 20212
- year
- 2022
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 9103264
- date added to LUP
- 2022-11-16 15:36:24
- date last changed
- 2022-11-17 03:40:00
@misc{9103264,
abstract = {{Traumatic brain injury (TBI) is one of leading causes of death in the world; survivors commonly exhibit behavioural changes and neurocognitive defects in the long-term. Following TBI, rapid changes in the neurovascular unit (NVU) occur as the permeability of the blood brain barrier (BBB) increases and cerebral blood flow (CBF) becomes dysregulated. An integral component of the NVU are pericytes which help maintain the integrity of the BBB, which are lost following mTBI resulting in BBB permeability and consequential leakage of blood plasma proteins into the brain parenchyma. After sustaining a TBI, females are more likely to develop persistent symptoms and show greater cognitive impairment than males. Importantly, the underlying causes for the differences in recovery following TBI are not well understood. Here, we investigate sex-specific differences following experimental TBI, by targeting capillary CD31 and Podocalyxin and pericyte PDGFrβ in the lateral cortex of mice with immunohistochemical and immunofluorescent techniques. Using an in vivo central fluid percussion injury (cFPI) model, male and female mice were analysed at day 2, 7 and 30 post-injury and were compared with controls. Our findings show that male capillaries and pericytes do not change following cFPI, whereas females showed a response in both capillaries and pericytes. Female mice exhibited reduced capillary width 30 days after cFPI as well as early phase response in pericytes. Our data suggests that sex-specific differences occur in capillaries and in pericytes following cFPI. Further research is required to determine the underlying mechanisms driving sex-specific responses, which may potentially lead to the development of sex-specific therapeutic interventions for TBI.}},
author = {{Fry, Christopher}},
language = {{eng}},
note = {{Student Paper}},
title = {{Sex-specific pathological response to Traumatic Brain Injury}},
year = {{2022}},
}