Nestin and small heat shock protein expression on reactive astrocytes and endothelial cells in cerebral abscess
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.
References (26)
- et al.
Astrocyte-derived VEGF mediates survival and tube stabilization of hypoxic brain microvascular endothelial cells in vitro
Brain Res. Dev. Brain Res.
(2001) - et al.
Nestin mRNA expression correlates with the central nervous system progenitor cell state in many, but not all, regions of developing central nervous system
Brain Res. Dev. Brain Res.
(1995) - et al.
Small heat shock proteins are molecular chaperones
J. Biol. Chem.
(1993) - et al.
Identification of a neural stem cell in the adult mammalian central nervous system
Cell
(1999) - et al.
Activation of protein kinase B (Akt/RAC-protein kinase) by cellular stress and its association with heat shock protein Hsp27
FEBS Lett.
(1997) - et al.
VEGF mRNA and its receptor flt-1 are expressed in reactive astrocytes following neural grafting and tumor cell implantation in the adult CNS
Exp. Neurol.
(1998) - et al.
Transient coexpression of nestin, GFAP, and vascular endothelial growth factor in mature reactive astroglia following neural grafting or brain wounds
Exp. Neurol.
(1999) - et al.
Inhibition of mitogen-activated protein kinase kinase blocks proliferation of neural progenitor cells
Brain Res. Dev. Brain Res.
(2000) - et al.
Survival, integration, and differentiation of neural stem cell lines after transplantation to the adult rat striatum
Exp. Neurol.
(1997) - et al.
Hsp27 as a switch between differentiation and apoptosis in murine embryonic stem cells
J. Biol. Chem.
(1997)
Shear stress activates cytosolic phospholipase A2 (cPLA2) and MAP kinase in human endothelial cells
Biochem. Biophys. Res. Commun.
Expression of vascular endothelial growth factor by reactive astrocytes and associated neoangiogenesis
Brain Res.
Fifteen-year review of the mortality of brain abscess
Neurosurgery
Cited by (14)
NPY mediates ATP-induced neuroproliferation in adult mouse olfactory epithelium
2010, Neurobiology of DiseaseCitation Excerpt :We found that ATP induces NPY release from neonatal mouse OE slices in vitro (Kanekar et al., 2009), suggesting that NPY may be involved in ATP-induced neuronal proliferation in neonatal mouse OE. NPY is a 36 amino acid peptide reported to induce neuronal precursor proliferation in subventricular zone of the lateral ventricle (Stanic et al., 2008), hippocampus (Ha et al., 2002; Howell et al., 2005) and retina (Milenkovic et al., 2004). In the OE, NPY is expressed in sustentacular cells (Hansel et al., 2001; Kanekar et al., 2009), and a subpopulation of microvillous cells, both of which have processes extending to the basement membrane (Kanekar et al., 2009; Montani et al., 2006), and in the olfactory ensheathing cells that reside in the lamina propria (Ubink et al., 1994).
Altered Nestin Expression in the Cerebrum With Periventricular Leukomalacia
2007, Pediatric NeurologyCitation Excerpt :We observed strong nestin immunoreactivity of glial cells, mostly astrocytes, in the white matter surrounding a lesion of periventricular leukomalacia (Table 3). This finding is not specific to periventricular leukomalacia, because re-expression of nestin by reactive astrocytes has been demonstrated for a variety of brain lesions [13-19]. Previous experimental studies using animal models have suggested that, in certain developmental stages, nestin-immunoreactive astrocytes may promote the regeneration of axons or permit the penetration of regrowing axons [29,30].
Nestin expression in pancreatic exocrine cell lineages
2004, Mechanisms of DevelopmentNestin <sup>+</sup> cells and healing the infarcted heart
2012, American Journal of Physiology - Heart and Circulatory PhysiologyClinicopathological correlations of nestin expression in surgically resectable pancreatic cancer including an analysis of perineural invasion
2011, Journal of Gastrointestinal and Liver Diseases