The locus coeruleus and cerebral metabolism: Recovery of function after cortical injury

Abstract

Cerebral metabolic effects of locus coeruleus (LC) lesion or drugs affecting LC were investigated after unilateral injury of sensorimotor cortex in rats. Sensoriomotor cortex ablation produced a widespread depression of cerebral 14C-2-deoxyglucose utilization which was reversed by amphetamine (AMP, 2 mg/kg) and worsened by haloperidol (HAL, 0.4 mg/kg). Lesion of LC alone did not affect cerebral oxidative metabolism, measured by a stain for the enzyme alphaglycerophosphate dehydrogenase (a-GPDH). Lesion of LC prior to undercut laceration of motor cortex shortened time to onset of a-GPDH cortical paling. Treatment with AMP (2 mg/kg) blocked cortical paling ofthe enzyme stain at 4 days postinjury, an effect prevented by concomitant HAL (0.3 or 0.6 mg/kg). Apomorphine (1 mg/kg) did not block cortical paling. These data parallel effects of these drugs on recovery of function. The results suggest that a metabolic "remote functional depression" (RFD) is alleviated by catecholamine activation after cortical injury, whereas onset of RFD is accelerated by LC lesions and exacerbated by catecholamine blockade.The locus coeruleus (LC) may have an important role in neuronal development and plasticity (Felton, Hallman,

Diaschisis.

“…19 In contrast, the depression of a-GPDH in the entire ipsilateral cortex following focal cortical injury 34 is exaggerated by lesions of the LC. 19 This data is compatible with the hypothesis that the LC "modulates" activity of other systems.…”

“…19 In contrast, the depression of a-GPDH in the entire ipsilateral cortex following focal cortical injury 34 is exaggerated by lesions of the LC. 19 This data is compatible with the hypothesis that the LC "modulates" activity of other systems. 35 In the rat, 6-hydroxydopamine-induced substantia nigra lesions have simulated the dopamine (DA) deafferentation of Parkinson's disease.…”

“…144 Selective cortical cell death without tissue necrosis could cause this metabolic depression; it occurs experimentally in penumbral areas, 143 ' 143 but appears rare in humans. l46> l47 Available metabolic data from experimental cortical ablation or freeze-lesions 19 ' l16 ' ll7 ' l48 " 130 suggest that intracortical diaschisis is of minor importance, perhaps because maintainence of a functional cortex depends on many afferents other than those from the cortical lesion site.…”

“…19 Unfortunately, because of the multiple (and many unknown) drug effects in injured brain, and lack of a strict relationship between structure (or neurotransmitter) and a single behavioral function, it is difficult to firmly ascertain the etiologic mechanisms of manipulated recovery.…”

Pharmacotherapy of aphasia. A critical review.

“…19 Such experimental stroke also causes widespread depression of glucose utilization in the cortex on both sides, the ipsilateral red nucleus, and the locus ceruleus bilaterally. 20 The postulated role of monoamines in stroke recovery led to a number of therapeutic studies in animal models, as summarized in Table 2. (In studies of recovery of function in animal models, it is useful to know that the duration of spontaneous recovery from a motor cortex lesion in a rat is about 2 weeks, and for a cat, spontaneous recovery takes several months.…”