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- Diab, Asim, et al.
(författare)
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Neutralization of macrophage inflammatory protein 2 (MIP-2) and MIP-1α attenuates neutrophil recruitment in the central nervous system during experimental bacterial meningitis
- 1999
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 67:5, s. 2590-2601
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Tidskriftsartikel (refereegranskat)abstract
- Chemokines are low-molecular-weight chemotactic cytokines that have been shown to play a central role in the perivascular transmigration and accumulation of specific subsets of leukocytes at sites of tissue damage. Using in situ hybridization (ISH), we investigated the mRNA induction of macrophage inflammatory protein 2 (MIP-2), MIP-1α, monocyte chemoattractant protein 1 (MCP-1), and RANTES. Challenge of infant rats’ brains with Haemophilus influenzae type b intraperitoneally resulted in the time-dependent expression of MIP-2, MIP-1α, MCP-1, and RANTES, which was maximal 24 to 48 h postinoculation. Immunohistochemistry showed significant increases in neutrophils and macrophages infiltrating the meninges, the ventricular system, and the periventricular area. The kinetics of MIP-2, MIP-1α, MCP-1, and RANTES mRNA expression paralleled those of the recruitment of inflammatory cells and disease severity. Administration of anti-MIP-2 or anti-MIP-1α antibodies (Abs) resulted in significant reduction of neutrophils. Administration of anti-MCP-1 Abs significantly decreased macrophage infiltration. Combined studies of ISH and immunohistochemistry showed that MIP-2- and MIP-1α-positive cells were neutrophils and macrophages. MCP-1-positive cells were neutrophils, macrophages, and astrocytes. Expression of RANTES was localized predominantly to resident astrocytes and microglia. The present study indicates that blocking of MIP-2 or MIP-1α bioactivity in vivo results in decreased neutrophil influx. These data are also the first demonstration that the C-C chemokine MIP-1α is involved in neutrophil recruitment in vivo.
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| 2. |
- Zhu, Li
(författare)
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Cerebrovascular disease and dementia : a population-based study
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Several vascular factors have been related to cognitive decline and dementia. One of the recent efforts has been focused on stroke, which could be prevented with appropriate measures. The data for this thesis were derived from the baseline and first follow-up of the Kungsholmen Project. All the officially registered inhabitants of the Kungsholmen district Stockholm, who were >= 75 years on October 1, 1987, were invited to participate in the project. Of all the eligible subjects, 1810 (76.4%) accepted to take part in the baseline survey. The DSM-III-R diagnostic criteria were used to define dementia. During 1992-94, a follow-up survey was conducted among the subjects who were free of dementia at baseline. The MMSE was also used as an indicator of cognitive decline in people without cognitive impairment and demented subjects respectively. APOE genotyping was assessed using standard PCR procedure from peripheral blood samples. Information on stroke was collected from the Stockholm inpatient register. The prevalence of both stroke and dementia increased with age. The prevalence of dementia among stroke survivors was 32.0%, which was higher than that (10.6%) among individuals without a history of stroke. Stroke was related to cognitive decline in people without cognitive impairment at baseline (OR = 1.9, 95% CI = 1.3-3.0). Recent stroke and APOE [epsilon]4 were each associated with an increased incidence of dementia (RR = 2.4, 95% CI = 1.5-3.9; RR = 1.7, 95% CI = 1.2-3.4, respectively). However, no synergistic effect was seen between these two factors on the risk of dementia. The RR of the interaction term was 1.2 (95% CI = 0.4-4.4, p = 0.7). APOE [epsilon]4 did not increase the risk of stroke in this Swedish elderly population (RR = 0.8, 95% CI = 0.5-1.5). We further studied the relationship between stroke and dementia by detecting the incidence of stroke in 1551 subjects who were free of stroke and did not have severe dementia at entry. Compared to subjects with MMSE >= 24, increased incidence of stroke was seen in the groups of people with mild dementia (RR = 2.6, 95% CI = 1.2-5.7) and cognitive impairment (RR = 2.0, 95% CI = 1.0-3.8). Finally, we found that use of antihypertensive medication, especially diuretics was related to a lower prevalence of dementia (OR = 0.4, 95% CI = 0.3-0.6), lower incidence of dementia (RR = 0.6, 95% CI = 0.4-0.9), and a slower cognitive decline (regression coefficient = -0.07, p = 0.04) in demented patients. In conclusions, recent stroke is a risk factor for dementia in the elderly. There is no synergistic effect between stroke and APOE [epsilon]4 on the risk of dementia. The presence of silent brain infarction may explain the increased risk of stroke in people with mild dementia or cognitive impairment. Antihypertensive drugs, especially diuretics can protect against dementia, probably by reducing the occurrence of cerebrovascular lesions.
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