Regional Sensitivity to Neuroinflammation: In Vivo and In Vitro Studies
Neuroinflammation is involved in several acute-onset neuropathologies such as meningitis, encephalitis, stroke, and traumatic brain injury as well as in neurodegenerative diseases. All of these patholologies are associated with cognitive deficits. Using a model of pure neuroinflammation (intracisternal injection of endotoxin in mice), we tested the hypothesis that brain regions involved in cognition are the most vulnerable to inflammatory insults, and this vulnerability is an inherent property of neocortical neurons. Mice (n = 10/group) injected with endotoxin (LPS) or saline in the cisterna magna underwent neurobehavioral and cognitive testing followed by quantitative autoradiographic assessment of regional neuroinflammation with [3H]PK11195, an established marker of microgliosis. In parallel, cocultures of cortical and striatal neurons taken from embryonic day 19 rat embryos or postnatal day 1 mice expressing green fluorescent protein were exposed for 24 h to the proinflammatory cytokine TNFalpha, glutamate, or a combination of the two agents. LPS-treated mice exhibited significant deficits in memory and significant increases in specific PK11195 binding in cortical and hippocampal regions, but not in striatum. Cultured neurons of cortical origin showed significantly lower survival rate relative to striatal neurons in response to TNFalpha, glutamate, or a combination of the two agents. Furthermore, TNFalpha exerted neuroprotective rather than neurotoxic effects in the striatal but not in the cortical neurons. These results suggest that the cortex is inherently more sensitive than the striatum to the deleterious effects of neuroinflammation, and may offer an explanation for the preponderance of cognitive deficits in neuropathologies with a neuroinflammatory component.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Sponsoring Organization:
- DOE - OFFICE OF SCIENCE
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 1014363
- Report Number(s):
- BNL-95126-2011-JA; R&D Project: MO-085; KP1602010; TRN: US1102744
- Journal Information:
- Synapse, Vol. 65, Issue 7
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
BRAIN
DISEASES
EMBRYOS
ENCEPHALITIS
ENDOTOXINS
HYPOTHESIS
IN VITRO
IN VIVO
LYMPHOKINES
MICE
NERVE CELLS
ORIGIN
PROTEINS
SENSITIVITY
TESTING
VULNERABILITY
neuroinflammation
regional sensitivity
autoradiography
cognitive deficits
LPS (endotoxin)
peripheral benzodiazepine receptors
translocation protein