Dynamics of rabbit brain edema in focal lesion and perilesion area after traumatic brain injury: a MRI study.
ABSTRACT Abstract To understand the dynamics of brain edema in different areas after traumatic brain injury (TBI) in rabbit, we used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) to monitor blood-brain barrier (BBB) permeability and cytotoxic brain edema after weight drop-induced TBI in rabbit. The dynamics of BBB permeability and brain edema were quantified using K(trans) and apparent diffusion coefficient (ADC) in the focal and perifocal lesion areas, as well as the area contralateral to the lesion. In the focal lesion area, K(trans) began to increase at 3 h post-TBI, peaked at 3 days, and decreased gradually while remaining higher than sham injury animals at 7 and 30 days. ADC was more variable, increased slightly at 3 h, decreased to its lowest value at 7 days, then increased to a peak at 30 days. In the perifocal lesion area, K(trans) began to increase at 1 day, peaked at 3-7 days, and returned to control level by 30 days. ADC showed a trend to increase at 1 day, followed by a continuous increase thereafter. In the contralateral area, no changes in K(trans) and ADC were observed at any time-point. These data demonstrate that different types of brain edema predominate in the focal and perifocal lesion areas. Specifically cytotoxic edema was predominant in the focal lesion area while vasogenic edema predominated in the perifocal area in acute phase. Furthermore, secondary opening of the BBB after TBI may appear if secondary injury is not controlled. BBB damage may be a driving force for cytotoxic brain edema and could be a new target for TBI intervention.
- SourceAvailable from: John A Butman[show abstract] [hide abstract]
ABSTRACT: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is widely used to evaluate tumor permeability, yet measurements have not been directly validated in brain tumors. Our purpose was to compare estimates of forward leakage K(trans) derived from DCE-MRI to the estimates K obtained using [(14)C]aminoisobutyric acid quantitative autoradiography ([(14)C]AIB QAR), an established method of evaluating blood-tumor barrier permeability. Both DCE-MRI and [(14)C]AIB QAR were performed in five rats 9 to 11 days following tumor implantation. K(trans) in the tumor was estimated from DCE-MRI using the threeparameter general kinetic model and a measured vascular input function. K(i) was estimated from QAR data using regions of interest (ROI) closely corresponding to those used to estimate K(trans). K(trans) and K(i) correlated with each other for two independent sets of central tumor ROI (R = 0.905, P = .035; R = 0.933, P = .021). In an additional six rats, K(trans) was estimated on two occasions to show reproducibility (intraclass coefficient = 0.9993; coefficient of variance = 6.07%). In vivo blood-tumor permeability parameters derived from DCE-MRI are reproducible and correlate with the gold standard for quantifying blood tumor barrier permeability, [(14)C]AIB QAR.Neoplasia (New York, N.Y.) 08/2007; 9(7):546-55. · 5.48 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: The importance of glial cell-propagated inflammation (i.e., neuroinflammation) disorders such as Alzheimer's disease (AD) was viewed previously as a bystander effect, or epiphenomenon, with inflammation occurring when damaged neurons elicit an activation response by glia. However, an accumulating body of evidence has challenged this earlier perspective and indicates a more active role of neuroinflammation in the pathophysiology of progressive neurodegenerative disorders such as AD, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. This insight into pathophysiology evolved in concert with the appreciation that the brain is not as immunologically privileged as once thought. The central nervous system (CNS) has its own resident immune system, in which glial cells (microglia, astrocytes, and oligodendrocytes) not only serve supportive and nutritive roles for neurons but also engage from time to time in several "inflammatory" processes that defend the CNS from pathogens and help it to recover from stress and injury. These otherwise "normal" glial functions can sometimes result in a more severe and chronic neuroinflammatory cycle that actually promotes or propagates neurodegenerative disease. Excessive glial cell activation may thus constitute a viable target for the discovery of and development of neurodegenerative disease therapeutics. Suggestive clinical evidence in support of neuroinflammation as a drug discovery target for chronic neurodegenerative diseases, such as AD, comes from epidemiological and genetic linkage data. For example, long-term use of nonsteroidal anti-inflammatory drugs is correlated with a protective effect against AD, and certain polymorphisms in the genes for interleukin 1 and other proinflammatory mediator genes are associated with increased risk. In AD and Parkinson's disease, activated microglia and complement proteins have been identified in the brain regions most affected in these disorders. This report will briefly review selected clinical and preclinical data that reflect the prevailing approaches targeting neuroinflammation as a pathophysiological process contributing to the onset or progression of neurodegenerative diseases, as well as their neuroprotective potential.Annals of the New York Academy of Sciences 01/2008; 1122:23-34. · 4.38 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Pharmacological studies using bradykinin B2 receptor antagonists suggest that bradykinin, an early mediator of inflammation and the main metabolite of the kallikrein-kinin system, is involved in secondary brain damage after cerebral ischemia. However, the time-course of bradykinin production and kinin receptor expression as well as the conclusive role of bradykinin B2 receptors for brain damage after experimental stroke have not been elucidated so far. C57/Bl6 mice were subjected to 45 mins of middle cerebral artery occlusion (MCAO) and 2, 4, 8, 24, and 48 h later brains were removed for the analysis of tissue bradykinin concentration and kinin B2 receptor mRNA and protein expression. Brain edema, infarct volume, functional outcome, and long-term survival were assessed in WT and B2-/- mice 24 h or 7 days after MCAO. Tissue bradykinin was maximally increased 12 h after ischemia (three-fold), while kinin B2 receptor mRNA upregulation peaked 24 to 48 h after MCAO (10- to 12-fold versus naïve brain tissue). Immunohistochemistry revealed that kinin B2 receptors were constitutively and widely expressed in mouse brain, were upregulated 2 h after ischemia in cells showing signs of ischemic damage, and remained upregulated in the penumbra up to 24 h after ischemia. B2-/- mice had improved motor function (P<0.05), smaller infarct volumes (-38%; P<0.01), developed less brain edema (-87%; P<0.05), and survived longer (P<0.01) as compared with wild-type controls. The current results show that bradykinin is produced in the brain, kinin B2 receptors are upregulated on dying cells, and B2 receptors are involved in cell death and brain edema formation after experimental stroke.Journal of Cerebral Blood Flow & Metabolism 09/2005; 25(8):978-89. · 5.40 Impact Factor