Traumatic Brain Injury: Ultrastructural Features in Neuronal Ferroptosis, Glial Cell Activation and Polarization, and Blood–Brain Barrier Breakdown

The secondary injury process after traumatic brain injury (TBI) results in motor dysfunction, cognitive and emotional impairment, and poor outcomes. These injury cascades include excitotoxic injury, mitochondrial dysfunction, oxidative stress, ion imbalance, inflammation, and increased vascular permeability. Electron microscopy is an irreplaceable tool to understand the complex pathogenesis of TBI as the secondary injury is usually accompanied by a series of pathologic changes at the ultra-micro level of the brain cells. These changes include the ultrastructural changes in different parts of the neurons (cell body, axon, and synapses), glial cells, and blood–brain barrier, etc. In view of the current difficulties in the treatment of TBI, identifying the changes in subcellular structures can help us better understand the complex pathologic cascade reactions after TBI and improve clinical diagnosis and treatment. The purpose of this review is to summarize and discuss the ultrastructural changes related to neurons (e.g., condensed mitochondrial membrane in ferroptosis), glial cells, and blood–brain barrier in the existing reports of TBI, to deepen the in-depth study of TBI pathomechanism, hoping to provide a future research direction of pathogenesis and treatment, with the ultimate aim of improving the prognosis of patients with TBI.

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Blood-brain barrier dysfunction significantly correlates with serum matrix metalloproteinase-7 (MMP-7) following traumatic brain injury

NeuroImage Clinical ◽

10.1016/j.nicl.2021.102741 ◽

2021 ◽

pp. 102741

Author(s):

Paul Nichols ◽

Javier Urriola ◽

Stephanie Miller ◽

Tracey Bjorkman ◽

Kate Mahady ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Matrix Metalloproteinase ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Barrier Dysfunction ◽

Blood Brain ◽

Matrix Metalloproteinase 7

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ELEVATION OF MATRIX METALLOPROTEINASES 3 AND 9 IN CEREBROSPINAL FLUID AND BLOOD IN PATIENTS WITH SEVERE TRAUMATIC BRAIN INJURY

Neurosurgery ◽

10.1227/01.neu.0000351768.11363.48 ◽

2009 ◽

Vol 65 (4) ◽

pp. 702-708 ◽

Cited By ~ 95

Author(s):

Mark Grossetete ◽

Jeremy Phelps ◽

Leopold Arko ◽

Howard Yonas ◽

Gary A. Rosenberg

Keyword(s):

Traumatic Brain Injury ◽

Cerebrospinal Fluid ◽

Brain Injury ◽

Matrix Metalloproteinases ◽

Blood Brain Barrier ◽

Normal Pressure Hydrocephalus ◽

Normal Pressure ◽

Brain Barrier ◽

Western Immunoblot ◽

Blood Brain

Abstract OBJECTIVE Traumatic brain injury (TBI) causes an increase in matrix metalloproteinases (MMPs), which are associated with neuroinflammation, blood-brain barrier disruption, hemorrhage, and cell death. We hypothesized that patients with TBI have an increase in MMPs in ventricular cerebrospinal fluid (CSF) and plasma. METHODS Patients with TBI and a ventricular catheter were entered into the study. Samples of CSF and plasma were collected at the time of catheter placement and at 24 and 72 hours after admission. Seven TBI patients were entered into the study, with 6 having complete data for analysis. Only patients who had a known time of insult that fell within a 6-hour window from initial insult to ventriculostomy were accepted into the study. Control CSF came from ventricular fluid in patients undergoing shunt placement for normal pressure hydrocephalus. Both MMP-2 and MMP-9 were measured with gelatin zymography and MMP-3 with Western immunoblot. RESULTS We found a significant elevation in the levels of the latent form of MMP-9 (92-kD) in the CSF obtained at the time of arrival (P < 0.05). Elevated levels of MMP-2 were detected in plasma at 72 hours, but not in the CSF. Using albumin from both CSF and blood, we calculated the MMP-9 index, which was significantly increased in the CSF, indicating endogenous MMP production. Western immunoblot showed elevated levels of MMP-3 in CSF at all times measured, whereas MMP-3 was not detected in the CSF of normal pressure hydrocephalus. CONCLUSION We show that MMPs are increased in the CSF of TBI patients. Although the number of patients was small, the results were robust and clearly demonstrated increases in MMP-3 and MMP-9 in ventricular CSF in TBI patients compared with controls. Although these preliminary results will need to be replicated, we propose that MMPs may be important in blood-brain barrier opening and hemorrhage secondary to brain injury in patients.

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