Elsevier

Neuroscience Research

Volume 44, Issue 2, October 2002, Pages 207-212
Neuroscience Research

Nestin and small heat shock protein expression on reactive astrocytes and endothelial cells in cerebral abscess

https://doi.org/10.1016/S0168-0102(02)00126-8Get rights and content

Abstract

Cerebral abscess results in an extensive capsular formation, which is an important limiting barrier for the spread of microorganism. Reactive astrocytes and endothelial cells are major cellular components of the abscess capsule together with fibrocytes. Molecular pathogenesis that results in the migration and proliferation of these cells remain speculative. Intermediate filament (IF) nestin and small heat shock proteins (sHSP) are developmentally regulated protein. In this study, we found that nestin expression is re-induced in not only reactive astrocytes, but also in endothelial cells in the gliotic area of the capsule. These nestin expressing astrocytes and endothelial cells also expressed sHSPs, such as heat shock protein 27 (HSP27) and αB-crystalline. These results indicated that embryonic reversions of cytoskeletal proteins to nestin and the increased expression of sHSPs in in reactive astrocytes and endothelial cells are caused by pathogenic microorganism induced inflammatory stress.

Introduction

Cerebral abscesses are caused by a wide variety of bacteria, fungi, and parasites. An abscess is initiated when microorganisms are introduced into cerebral tissues, as a result of trauma, contiguous infection, or hematogenous dissemination (Takeshita et al., 1997). The progressive histologic changes that accompany a developing brain abscess have been described (Britt et al., 1981). Capsule formation is the single most important event that limits the spread of infection, and thus prevents the destruction of brain parenchyma (Britt et al., 1981). Furthermore, therapeutic interventions that increase early capsule formation may be adjuncts in the management of cerebral abscess. Capsule formation is influenced by a number of factors. It is well known that poorer vascularity of the deep white matter and coagulase producing anaerobic organisms retard capsule formation (Alderson et al., 1981). Fibrocytes, reactive astrocytes and proliferating capillary endothelial cells are the main cellular components of the capsule, and increased vascularity and gliosis help prevent the spread of microorganisms. Understanding the exact molecular mechanisms, with respect to these cellular components that are affected by cerebral abscesses, will help us to plan therapeutic strategies.

Intermediate filaments (IFs) play a role in cell integrity, mobility, differentiation, and provide protection and tissue structure that resists mechanical stress (Salvador-Silva et al., 2001). The sequential expression of neuronal cytoskeletal proteins is developmentally regulated in concert with migration (Zerlin et al., 1995). A type six intermediate filament protein nestin is transiently expressed in neuroepithelial stem cells and radial glia during the neurulation and migratory stages of cortical development, respectively (Lundberg et al., 1997). Moreover, the differentiation of multipotent stem cells into postmitotic neurons and glial cells is accompanied by the downregulation of nestin and the expression of mature intermediate filaments (Loo et al., 1994). More recently, it has been demonstrated that nestin-expressing stem cells have the potential to migrate to sites of injury and differentiate into mature neuron and glial cells (Johansson et al., 1999). IF nestin has also been demonstrated in adult reactive astrocytes in the presence of kainic acid lesions in the hippocampus and direct brain trauma. The re-expression of an embryonic marker in reactive astrocytes suggests a morphological plasticity or of a method of enhancing functional recovery (Frisen et al., 1995), but the exact nature of this alteration remains speculative.

Small heat shock proteins (sHSP) are induced in response to different stresses including heat shock, oxidative stress, metal ions and cytokines (Konishi et al., 1997). αB-crystallin and heat shock protein 27 kDa (Hsp27) are members of the sHSP family, with molecular masses of approximately 22 and 27 kDa, respectively. sHSPs function as molecular chaperons and participate in protein folding, translocation, interaction and the turnover of cytoskeletal proteins under developmental periods or during stress (Che et al., 2001).

To define the effect of the inflammatory stress caused by cerebral abscesses on the brain parenchyma, we examined the synthesis and cellular distribution of sHSPs and nestin in the zone of gliosis. We used immunohistochemical analysis to study the expression of nestin, HSP 27, and αB-crystalline in surgical specimens with a confirmed abscess.

Section snippets

Material and methods

Ten consecutive collected surgical specimens meeting the histological criteria for cerebral abscess were identified from the database of the Yonsei Medical Center. Clinical records and surgical reports were reviewed for clinical information, including the age of patients at the time of surgery, patient sex, location, and the mode of presentation. Control brain specimens were isolated from neocortex of temporal lobe epilepsy patients and corpses that were offered from national institute of

Clinical findings

The clinical characteristics of the ten patients are summarized in Table 1. These ten patients (four females and six males) each with a cerebral abscess comprised the study population.

At the time of surgery the patients ranged in age from 1 to 63 years (mean 24.5 years). Eight patients had associated pathological conditions, such as liver disease, diabetes, congenital heart disease, and head injury. Seven lesions were localized to the frontal lobe, two to the temporal, and one to the parietal.

Discussion

In this study, we found that astrocytes and endothelial cells in abscess capsules continue in their protective role by expressing developmental proteins, such as nestin and sHSP. Capsule formation is the most significant change that occurs during the late cerebritis phase (Britt et al., 1981). Pus formed enlarged necrotic centers are circumscribed by collagen tissues. Infiltrating inflammatory cells and migrating activated astrocytes and endothelial cells are found within the capsule and in the

Conclusion

In this study, we observed that astrocytes and endothelial cells express developmental proteins in the presence of a cerebral abscess. The functional significance of induced developmental protein expressions might have a protective function against infection. The early activation of astrocytes and endothelial cells should be helpful to prevent microorganism spread.

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