摘要:

ABSTRACTMajor infections, such as sepsis and pneumonia, occur in 50–75% of patients following isolated severe head injury. Previous studies have demonstrated that this high incidence of infection following severe head injury may be related to a decrease in helper T-cell activation and function.The present study was designed to investigate the effect of severe head injury on specific subgroups of helper T cells known to enhance or suppress cellular immune function. Specifically, peripheral blood lymphocytes (PBLs) from 10 head-injured patients and 10 matched controls were evaluated following in vitro stimulation with the T-cell mitogen, phytohemagglutinin (PHA). Subsets of helper T cells evaluated included activated helper (CD4+/CD25+) T cells; helper/inducer (CD4+/CDw29+) T cells, which enhance cellular immune activity; and suppressor/inducer (CD4+/CD45R+) T-cells, which induce suppressor (CD8+) T-cells. In addition, the effect of intraventricular fluid (IVF) on PHA-stimulated in vitro CD4 and CD25 expression was investigated to determine whether severe head injury results in the production of mediators within the central nervous system capable of affecting T-cell activation.The results of this study indicate that isolated severe head injury selectively reduces the ability of PHA-stimulated PBLs to express the helper/inducer (CD4+/CDw29+) T-cell (p = 0.023) and activated helper (CD4+/CD25+) T-cell (P = 0.041) phenotypes. There was no significant change in PHA-stimulated CD4 or CD25 expression following incubation of PBLs with intraventricular fluid (IVF) from head-injured patients. The relationshp between these changes in specific helper T-cell subpopulations and the infectious complications of severe head injury are discusse

ISSN:0897-7151    

DOI:10.1089/neu.1992.9.1

年代:1992

数据来源: MAL

摘要:

ABSTRACTTraumatic brain injury produces significant cognitive deficits in humans. This experiment used a controlled cortical impact model of experimental brain injury to examine the effects of brain injury on spatial learning and memory using the Morris water maze task. Rats (n= 8) were injured at a moderate level of cortical impact injury (6 m/sec, 1.5–2.0 mm deformation). Eight additional rats served as a sham-injured control group. Morris water maze performance was assessed on days 11–15 and 30–34 following injury. Results revealed that brain-injured rats exhibited significant deficits (p<0.05) in maze performance at both testing intervals. Since the Morris water maze task is particularly sensitive to hippocampal dysfunction, the results of the present experiment support the hypothesis that the hippocampus is preferentially vulnerable to damage following traumatic brain injury. These results demonstrate that controlled cortical impact brain injury produces enduring cognitive deficits analogous to those observed after human brain i

ISSN:0897-7151    

DOI:10.1089/neu.1992.9.11

年代:1992

数据来源: MAL

摘要:

ABSTRACTExperimental brain injury is associated with marked vasogenic edema, as evidenced by an increase in brain water content. This prominent and widespread response raises questions about the vulnerability of microvasculature in the brain to injury. In the present report we further characterize the vascular response by evaluating the integrity of the blood–brain barrier to circulating proteins.Vascular permeability to endogenous immunoglobulins (IgG) and to the protein horseradish peroxidase (HRP) was examined after a lateral, fluid percussive brain injury in the rat. In study 1 IgG was immunolocalized in brain sections 1–24 hr after injury. In studies 2 and 3 HRP was given intravenously either before impact (study 2) or 10 min before sacrifice (study 3). Permeability to this protein was assessed at 1–6 hr (study 2) or at 1–72 hr (study 3) after injury.In studies 1 and 2 the extravascular accumulation of proteins was evaluated. Pronounced abnormal permeability to IgG and HRP occurred within the first hour after injury and was widespread throughout both hemispheres. The intensity of immunostaining for IgG increased with time up to 24 hr after injury. In contrast, maximal extravascular accumulation of HRP occurred within the first hour after injury.In study 3 the time course for re-establishment of the blood–brain barrier to HRP was determined. Maximal permeability occurred at 1 hr after injury. At 24 hr abnormal permeability was restricted to the impact site and this area remained permeable up to 72 hr after injury.In summary this study demonstrates that breakdown of the blood–brain barrier to plasma proteins is a prominent feature of experimental brain injury. This abnormal permeability is characterized by its transient expression and widespread distribution. The time course for re-establishment of the blood–brain barrier to circulating proteins is most delayed at th

ISSN:0897-7151    

DOI:10.1089/neu.1992.9.21

年代:1992

数据来源: MAL

摘要:

ABSTRACTThe present study evaluated the effect of the nonglucocorticoid 21-aminosteroid U74006F, an inhibitor of iron-dependent lipid peroxidation, on the development of regional cerebral edema after lateral fluid-percussion (FP) brain injury. Male Sprague-Dawley rats (n= 40) were anesthetized and subjected to FP brain injury of moderate severity centered over the left parietal cortex (2.5–2.6 atms). Fifteen minutes after brain injury, animals randomly received an i.v. bolus of either U74006F (3 mg/kg,n= 21) followed by a second bolus (3 mg/kg) at 3 hr or buffered sodium citrate vehicle (equal volume,n= 15). An additional group of 12 surgically prepared but uninjured animals served as preinjury controls. At 48 hr after injury, animals were sacrificed and brain tissue assayed for water content and regional cation concentrations. With the use of specific gravimetric techniques, no significant differences were observed in posttraumatic cerebral edema between drug- and control-treated animals. However, using wet weight/dry weight methodology, we found that administration of U74006F significantly reduced water content in the right hippocampus (contralateral to the site of injury) compared to saline-treated animals (p<0.05). U74006F also significantly prevented the postinjury increase in sodium concentrations in the ipsilateral hippocampus (p<0.05) and thalamus (p<0.03). Regional concentrations of potassium were unaltered after drug treatment. Administration of U74006F significantly reduced postinjury mortality, from 28% in control animals to zero in treated animals (p = 0.01). These results suggest that lipid peroxidation may be involved in the pathophysiological sequelae of brain injury and that 21-aminosteroids may be beneficial in the treatment of brain injur

ISSN:0897-7151    

DOI:10.1089/neu.1992.9.33

年代:1992

数据来源: MAL

摘要:

ABSTRACTTissue damage involving oxygen-derived free radicals may be greatly exacerbated by free, reactive iron, which acts as a catalyst in oxidative reactions. The effects of free iron can be attenuated by the administration of deferoxamine (DFO), an iron chelator. However, DFO has limited therapeutic utility because it has a short plasma half-life (approximately 5.5 min in mice) and produces profound hypotension upon intravenous infusion. These negative attributes have been circumvented by the covalent attachment of DFO to large polymers, such as dextran or hydroxyethyl starch. The ability of the dextran-conjugated DFO (DEX-DFO) to inhibit iron-catalyzed reactions with lipids was compared to that of the native molecule in an in vitro model of CNS lipid degradation in the presence of 200 μM ferrous iron. There was no difference between native DFO and the modified form. Modified and unmodified DFO were also compared for therapeutic efficacy in a murine model of head injury. Using a previously described "grip test" as a measure of neurologic impairment following injury, DEX-DFO, native DFO, and dextran were administered intravenously 3–5 min after injury. Dextran-DFO significantly decreased the incidence of severe neurologic impairment at dosage levels of 0.1 (n= 92), 1.0 (n= 76), and 10.0 (n= 80) mg/kg. Administration of native DFO or dextran had no effect at the same dosages and concentrations. These results suggest that the murine model of head injury contains a significant iron-dependent component that should be assessed in other models of neural inju

ISSN:0897-7151    

DOI:10.1089/neu.1992.9.47

年代:1992

数据来源: MAL

ISSN:0897-7151    

DOI:10.1089/neu.1992.9.55

年代:1992

数据来源: MAL