Release of spermidine from the rat cortex following permanent middle cerebral artery occlusion

Abstract

We have studied the effects of middle cerebral artery (MCA) occlusion in rats on polyamine efflux in the parietal cortex using the microdialysis technique. Dialysis probe implantation itself provoked a delayed, prolonged and vigorous release of spermidine and putrescine. Spermidine release returned to stable baseline levels within 48 hours. Putrescine release also returned to lower levels within this time period but putrescine levels in the dialysate fluctuated dramatically in individual animals. Because of the underlying effects of the dialysis probe (likely a reflection of traumatic cerebral damage and stimulation of polyamine metabolism and release within the immediate vicinity of the dialysis probe), MCA occlusion was performed 48 hours after probe implantation. MCA occlusion persistently (5/5 animals) resulted in a significant increase in cortical spermidine efflux, although the onset, magnitude and duration of this increased release was variable. Putrescine efflux was significantly increased in 2/5 animals with MCA occlusion but the increase in release was similar to the spontaneous fluctuations observed in control animals. Spermine was not detectable in cortical dialysates of control or MCA occluded groups. Spermidine, but not spermine or putrescine is consistently released from the parietal cortex following permanent focal ischaemia and may contribute to ischaemic neuropathology either through its effects at the N-methyl-D-aspartate (NMDA) receptor or via direct, and as yet uncharacterised, neurotoxic effects.

Neuroprotective role of ornithine decarboxylase activation in transient focal cerebral ischaemia: a study using ornithine decarboxylase-overexpressing transgenic rats

“…1991) and transgene‐expressed ODC (Halonen et al . 1993) together with the previous evidence that putrescine (Carter et al . 1995) and higher polyamines (Gilad et al .…”

“…There is ample evidence from syngenic (Paschen et al, 1987;Gilad & Gilad, 1991;Sauer et al, 1992) and ODC-transgenic animals (Lukkarinen et al, 1995(Lukkarinen et al, , 1997 unequivocally showing that ODC activity and putrescine concentration are strictly coupled before and after exposure to ischaemia. Neuronal localization of wild type (Müller et al, 1991) and transgene-expressed ODC (Halonen et al, 1993) together with the previous evidence that putrescine (Carter et al, 1995) and higher polyamines (Gilad et al, 1993) remain strictly intracellular during and after ischaemic energy failure, indicate that polyamines are acting in the cell interior. There are two major targets where polyamines and/or DFMO might act that deserve discussion.…”

Extracellular Spermine Exacerbates Ischemic Neuronal Injury through Sensitization of ASIC1a Channels to Extracellular Acidosis

“…It has been suggested that more polyamines could be released from necrotic neurons into the extracellular space and cause multiple effects (Li et al, 2007). This may also explain the observed lack of change (Carter et al, 1995; Baskaya et al, 1997) or decrease (Paschen et al, 1992) of spermine after cerebral ischemia in some studies, as polyamines released into the extracellular space may be cleared by the blood circulation. It is thus likely that sufficient spermine could influence the activation of ASICs during ischemia.…”

Conantokin G Is an NR2B-Selective Competitive Antagonist ofN-Methyl-d-aspartate Receptors

“…Polyamines are released in a calcium-dependent manner from neurons in response to chemical, electrical, or K ϩ stimulation (Harman and Shaw, 1981;Gilad and Gilad, 1991;Fage et al, 1992). Moreover, seizures and ischemia have been associated with an increase in polyamine levels (Hayashi et al, 1993;Carter et al, 1995). The activity-dependent release of polyamines may serve to enhance Con G block during periods of intense neuronal activity such as that occurring during seizures or stroke.…”