Blood–brain barrier permeability is positively correlated with cerebral microvascular perfusion in the early fluid percussion-injured brain of the rat

Abstract

The blood-brain barrier (BBB) opening following traumatic brain injury (TBI) provides a chance for therapeutic agents to cross the barrier, yet the reduction of the cerebral microvascular perfusion after TBI may limit the intervention. Meanwhile, optimizing the cerebral capillary perfusion by the strategies such as fluid administration may cause brain edema due to the BBB opening post trauma. To guide the TBI therapy, we characterized the relationship between the changes in the cerebral capillary perfusion and BBB permeability after TBI. First, we observed the changes of the cerebral capillary perfusion by the intracardiac perfusion of Evans Blue and the BBB disruption with magnetic resonance imaging (MRI) in the rat subjected to lateral fluid percussion (FP) brain injury. The correlation between two variables was next evaluated with the correlation analysis. Since related to BBB breakdown, matrix metalloproteinase-9 (MMP-9) activity was finally detected by gelatin zymography. We found that the ratios of the perfused microvessel numbers in the lesioned cortices were significantly reduced at 0 and 1 h post trauma compared with that in the normal cortex, which then dramatically recovered at 4 and 24 h after injury, and that the BBB permeability was greatly augmented in the ipsilateral parts at 4, 12, and 24 h, and in the contralateral area at 24 h after injury compared with that in the uninjured brain. The correlation analysis showed that the BBB permeability increase was related to the restoration of the cerebral capillary perfusion over a 24-h period post trauma. Moreover, the gelatin zymography analysis indicated that the MMP-9 activity in the injured brain increased at 4 h and significantly elevated at 12 and 24 h as compared to that at 0 or 1 h after TBI. Our findings demonstrate that the 4 h post trauma is a critical turning point during the development of TBI, and, importantly, the correlation analysis may guide us how to treat TBI.

Disruption of the blood–brain barrier in pigs naturally infected with Taenia solium, untreated and after anthelmintic treatment

“…It is tempting to speculate that post-treatment enhancement in MRI of the brain of patients, useful in their follow-up evaluation (Teitelbaum et al, 1989), may represent the same phenomenon of BBB dysfunction and, thus, could be considered equivalent to EB staining in our model. This correlation has been indeed tested and found positive ( r = 0.981, P = 0.019), comparing changes in the ratio of capillary number stained by EB and MRI signal intensity during traumatic brain injury (Lin et al, 2012). …”

bFGF Protects Against Blood-Brain Barrier Damage Through Junction Protein Regulation via PI3K-Akt-Rac1 Pathway Following Traumatic Brain Injury

“…BBB disruption results in uncontrolled efflux of ions and proteins from the intravascular space to the interstitial brain compartments with water accumulation, vasogenic brain edema, elevated intracerebral pressure, and secondary ischemic injuries [5]. Therefore, targeting the molecular mechanisms that regulate BBB permeability may lead to more efficacious therapeutic strategies for TBI [7, 8]. In the previous study, bFGF treatment shows the efficacy to reduce cerebral edema and neurological deficits after ischemia/reperfusion injury in stroke models [9].…”

Chronic global analysis of vascular permeability and cerebral blood flow after bone marrow stromal cell treatment of traumatic brain injury in the rat: A long-term MRI study

“…Considering the profiles presented by control group, the feature of staged evolution of Ki and CBF is consistent with previous findings. As revealed by the vast majority of investigations, BBB breakdown and hemodynamic disruption rapidly occur and persist in the early phase after TBI, with heterogeneously disturbed Ki and CBF detected in the injured brain both temporally and spatially (Engel et al, 2008; Li et al, 2016; Lin et al, 2012; Long et al, 2015; Su et al, 2015). Although gradually reversal of these pathologic changes are regionally observed in the follow-up period of time (such as 1-month post-TBI) (Villapol et al, 2014; Wei et al, 2012), compromised BBB integrity (Korn et al, 2005; Tomkins et al, 2008) as well as widespread hypoperfusion beyond the contusional lesion (including hippocampus, thalamus and perilesional regions) (Hayward et al, 2010; Liu et al, 2013) chronically persist.…”

“…To date, however, most research has primarily focused on either BBB leakage (Su et al, 2015; Tomkins et al, 2008; Wei et al, 2012; Yang et al, 2013) or perfusion deficits (Chen et al, 2013; Honda et al, 2016; Kaloostian et al, 2012; Kelly et al, 1997). There are few studies (Li et al, 2016; Lin et al, 2012) documenting the dynamic relationship between the degree of BBB damage and perfusion status post-injury, especially within a long period of time post-TBI and in a broad area of cerebral tissue. Knowledge of these interactions may facilitate a better understanding of their roles in mediating cerebral injurious and restorative processes.…”