Biomedical subjects

Sebastian Jander

Publications and source records attributed to Sebastian Jander.

22 records · Page 2Linked to original sources

PubMed2002

Detrimental and beneficial effects of injury-induced inflammation and cytokine expression in the nervous system.

Lesions in the nervous system induce rapid activation of glial cells and under certain conditions additional recruitment of granulocytes, T-cells and monocytes/macrophages from the blood stream triggered by upregulation of cell adhesion molecules, chemokines and cytokines. Hematogenous cell infiltration is not restricted to infectious or autoimmune disorders of the nervous system, but also occurs in response to cerebral ischemia and traumatic lesions. Neuroinflammation can cause neuronal damage, but also confers neuroprotection. Granulocytes occlude vessels during reperfusion after transient focal ischemia, while the functional role of T-cells and macrophages in stroke development awaits further clarification. After focal cerebral ischemia neurotoxic mediators released by microglia such as the inducible nitric oxide synthase (leading to NO synthesis) and the cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) are upregulated prior to cellular inflammation in the evolving lesion and functionally contribute to secondary infarct growth as revealed by numerous pharmacological experiments and by use of transgenic animals. On the other hand, cytokine induction remote from ischemic lesions involves NMDA-mediated signalling pathways and confers neuroprotection. After nerve injury T cells can rescue CNS neurons. In the peripheral nervous system neuroinflammation is a prerequisite for successful regeneration that is impeded in the CNS. In conclusion, there is increasing evidence that neuroinflammation represents a double edged sword. The opposing neurotoxic and neuroprotective properties of neuroinflammation during CNS injury provide arich and currently unexplored set of research problems.

Animals↗

PubMed2002

Dendritic cells and dendritic-like microglia in focal cortical ischemia of the mouse brain.

Intracerebral dendritic cells (DC) have recently been identified in neuroinflammation initiated peripherally by brain-targeted autoimmunity or infection. The present study detects DC in photochemically induced cortical ischemia of the mouse brain, a brain-intrinsic lesion model characterized by the lack of an overt T cell response. Concomitant to leukocyte infiltration of the infarcted area, cells expressing the pan-DC surface marker CD11c appeared at the lesion and persisted for weeks. These DC were located at the border zone of the infarct and remote from the lesion in degenerating corticothalamic fibre tracts and subcortical nuclei. All CD11c+ brain cells displayed a uniform CD11b+/CD8alpha-/CD205- surface phenotype, indicating a myeloid origin, and were immature DC based on their MHC class II+/CD40-/CD80+/CD86+/- profile. By expressing high levels of CD45, most DC from ischemic brain seemed to be blood-derived while a minority were CD45(low), thus corresponding to resident microglia. Consistently, round-shaped CD11c+ cells were found at the lesion whereas CD11c+ cells at subcortical sites were ramified like parenchymal microglia. These findings evidence a recruitment of myeloid DC to ischemic brain lesions and suggest that reactive microglia in remote areas transform into dendritic-like cells. Brain-infiltrating DC and their microglial counterparts may play a role in the inflammatory response to cerebral ischemia independently of T cells.

Animals↗

PubMed2002

Degeneration and regeneration of the peripheral nervous system: from Augustus Waller's observations to neuroinflammation.

This review article on the degeneration and regeneration of peripheral nerve fibers was presented as a Plenary Lecture at the 2001 meeting of the Peripheral Nerve Society. It is accompanied by a reprint of Augustus Waller's 1850 article, which gave rise to the pathologic process termed Wallerian degeneration. This review is focused on the role of neuroinflammation in Wallerian degeneration and how immune mediators contribute to both axonal degeneration and regeneration. Similarities and differences between the PNS and CNS in terms of inflammation and microglial activation after nerve injury are discussed, and point towards progress in understanding the failure of nerve fiber regeneration in the CNS.

Humans↗

PubMed2002

Interleukin-18 expression after focal ischemia of the rat brain: association with the late-stage inflammatory response.

Interleukin-18, previously designated interferon gamma-inducing factor, is a proinflammatory cytokine structurally related to interleukin-1beta and is therefore considered a member of the growing family of interleukin-1-like cytokines. Both interleukin-18 and -1beta are synthesized as inactive precursors that necessitate cleavage by caspase-1 for functional activity. In this study, the authors analyzed the expression pattern of interleukin-18, -1beta, and caspase-1 in focal brain ischemia induced in rats either by permanent middle cerebral artery occlusion or by photothrombosis of cortical microvessels. Using reverse transcriptase-polymerase chain reaction, they found a delayed increase of interleukin-18 mRNA starting at 48 hours and reaching its peak between 7 and 14 days after ischemia. In contrast, interleukin-1beta mRNA peaked within 16 hours and was downregulated thereafter. The time course of caspase-1 mRNA expression paralleled that of interleukin-18, but not of interleukin-1beta mRNA. Immunocytochemically, interleukin-18 expression was localized to ED1-positive phagocytic microglia/macrophages infiltrating the necrotic lesion between 3 and 6 days after ischemia. In contrast, interleukin-1beta immunoreactivity was expressed by ramified microglia in the infarct border zone and remote ipsilateral cortex during the first 16 hours postlesion. Induction of interleukin-18 was not accompanied by detectable expression of interferon-gamma mRNA. Their data show spatial and temporal diversity in interleukin-1 and -18 cytokine family expression in brain ischemia, and suggest a role of the interleukin-18/caspase-1 pathway in late-stage inflammatory responses to focal brain ischemia.

Animals↗