Downregulation of in vitro neurotoxicity of brain macrophages by prostaglandin E₂ and a β‐adrenergic agonist

Abstract

Brain macrophages (BM), a subpopulation of microglia, have the ability to kill neurons by producing reactive oxygen intermediates. Cocultures of neurons and macrophages derived from the cerebral cortex of rat embryos were used to look for regulation of BM neurotoxicity. Isoproterenol (10(-7) M), a beta-adrenergic agonist, induced a significant inhibition of BM neurotoxicity and this effect was abolished in the presence of propranolol, a beta-adrenergic antagonist. BM neurotoxicity was also reduced in the presence of prostaglandin E2 (10(-8), 10(-6) M), a metabolite derived from arachidonic acid. These results suggest endogenous mechanisms of neuroprotection operating either during development or following lesions.

Long-term elevation of cyclooxygenase-2, but not lipoxygenase, in regions synaptically distant from spreading depression

“…Previous work from this laboratory (Caggiano and Kraig, 1996) has shown that blockade of lipoxygenase enzymes retards the induction of reactivity in microglia, whereas cyclooxygenase inhibition may enhance the induction of reactivity in microglia. In addition, neurotoxicity by brain macrophages is reduced by COX products (Thery et al, 1994). These results suggest that both LIPOX and COX-2 are involved in brain inflammation, possibly serving pro-inflammatory and protective roles, respectively.…”

Non-steroidal anti-inflammatory drugs in Parkinson's disease

“…Indeed, in spite of its classic role as a pro-inflammatory molecule, several recent in vitro observations indicate that prostaglandin E2 can inhibit microglial activation. At lower (nanomolar) concentrations, PGE 2 protects hippocampal and cortical neuronal cultures against excitotoxic injury or LPS-induced cytotoxicity (Akaike et al, 1994;Thery et al, 1994;Kim et al, 2002;McCullough et al, 2004). The protective effect of EP 2 receptor activity has been confirmed in vivo, in a model of transient forebrain ischemia, in which the genetic deletion of this PGE 2 receptor exacerbates the extent of neuronal damage (McCullough et al, 2004).…”

Induction of resting microglia in culture medium devoid of glycine and serine

“…A number of in vitro studies have demonstrated that microglial cells are potentially harmful to neurons, because microglial cells can produce and secrete neurotoxic agents including reactive oxygen (O 2 -, H 2 O 2 ) Théry et al, 1991Théry et al, , 1994, reactive nitrogen (NO, ONOO -) Chao et al, 1992), glutamate (Piani et al, 1991), quinolinic acid (Heyes et al 1996), and an unidentified heat-stable, protease-resistant factor with a low molecular weight (Giulian et al, 1993;Vaca and Wendt, 1992). On the other hand, several in vivo studies have shown the beneficial effects of microglial cells on neurons.…”