The nature of the chick's magnesium‐sensitive retinal spreading depression

Harreveld, A. Van

doi:10.1002/neu.480150504

Cited by 51 publications

(28 citation statements)

References 23 publications

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“…pO 2 of 140 mmHg (corresponding to ∼20% oxygen) was maintained in the gas phase directly above the retinas. Under our experimental conditions, 6 mM MgCl 2 (n = 20) completely suppressed SD, as reported (18).…”

Section: Resultssupporting

confidence: 85%

See 1 more Smart Citation

Reentrant spiral waves of spreading depression cause macular degeneration in hypoglycemic chicken retina

Yu¹,

Santos²,

Mattiace³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Spreading depression (SD), a slow diffusion-mediated self-sustained wave of depolarization that severely disrupts neuronal function, has been implicated as a cause of cellular injury in a number of central nervous system pathologies, including blind spots in the retina. Here we show that in the hypoglycemic chicken retina, spontaneous episodes of SD can occur, resulting in irreversible punctate lesions in the macula, the region of highest visual acuity in the central region of the retina. These lesions in turn can act as sites of origin for secondary self-sustained reentrant spiral waves of SD that progressively enlarge the lesions. Furthermore, we show that the degeneration of the macula under hypoglycemic conditions can be prevented by blocking reentrant spiral SDs or by blocking caspases. The observation that spontaneous formation of reentrant spiral SD waves leads to the development of progressive retinal lesions under conditions of hypoglycemia establishes a potential role of SD in initiation and progression of macular degeneration, one of the leading causes of visual disability worldwide.diabetes | retinal migraine | scotomas C urrent research has revealed a number of molecular mechanisms underlying the pathophysiology of macular degeneration (1), a disease that involves damage to the central retina, where the higher density of photoreceptors results in maximal visual acuity (2). Macular degeneration is a leading cause of visual disability (1, 2). However, the reasons for the particular sensitivity of the macula remain speculative. A number of patients report the presence of monocular scotomas that gradually enlarge and move across the retinal field, and this phenomenon, which can lead to loss of vision, has been ascribed to retinal migraine (3, 4). Although the occurrence of retinal migraine has been disputed (5), the likely cause is spreading depression (SD), a phenomenon initially described in the central nervous system by Leão (6). SD is a slow diffusion-mediated self-sustained wave of generalized depolarization of gray matter or retina that does not respect synaptic connectivity (7) and severely disrupts neuronal function. SD results in a temporary collapse of transmembrane ionic gradients and membrane potential (8, 9), and is characterized by a negative field potential 10-20 mV in amplitude and 1-2 min in duration, propagating at a velocity of a few millimeters per minute (6-10). The advancing wave front is accompanied by a burst of action potentials and K + efflux into the interstitial space, followed by electrical silence, which is associated with the negative field potential (11, 12). Na + and Cl − enter the cells, causing an influx of water, swelling, and reduction in the volume of the extracellular space. In addition, proinflammatory compounds are released, often accompanied by edema and extravasation of blood proteins (13). Recovery can occur in minutes, but repeated episodes of SD increase neuronal loss surrounding traumatic brain lesions, and have been implicated in other central nervous syst...

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Section: Resultssupporting

confidence: 85%

“…TTX, which does not block SD (8), did not prevent SD-induced cell death (n = 8). Both MgCl 2 and halothane blocked initiation of SD waves (18,21) and prevented development of punctate lesions and lesion expansion (Figs. 3 B and C and 4B), as well as activation of caspase 3 ( Fig.…”

Section: Mechanisms Whereby Hypoglycemia Leads To Reentrant Spiral Sdmentioning

confidence: 94%

Reentrant spiral waves of spreading depression cause macular degeneration in hypoglycemic chicken retina

Yu¹,

Santos²,

Mattiace³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…In comparison to control subjects, the levels of magnesium (Mg), measured with 31 pNMR were found significantly lower in the brain of migraine patients, particularly during migraine attacks [17]. Mg is the unique compound known to block glutamate-dependent SD [18]. Lamotrigine is an antiepileptic drug acting by blocking voltage-sensitive channels leading to an inhibition of glutamate release [19].…”

Section: Glutamate and Auramentioning

confidence: 98%

Biochemistry of primary headaches: role of tyrosine and tryptophan metabolism

D’Andrea¹,

Cevoli

Colavito³

et al. 2015

Neurol Sci

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The pathogenesis of migraine as well as cluster headache (CH) is yet a debated question. In this review, we discuss the possible role of the of tyrosine and tryptophan metabolism in the pathogenesis of these primary headaches. These include the abnormalities in the synthesis of neurotransmitters: high level of DA, low level of NE and very elevated levels of octopamine and synephrine (neuromodulators) in plasma of episodic migraine without aura and CH patients. We hypothesize that the imbalance between the levels of neurotransmitters and elusive amines synthesis is due to a metabolic shift directing tyrosine toward an increased decarboxylase and reduced hydroxylase enzyme activities. The metabolic shift of the tyrosine is favored by a state of neuronal hyperexcitability and a reduced mitochondrial activity present in migraine. In addition we present biochemical studies performed in chronic migraine and chronic tension-type headache patients to verify if the same anomalies of the tyrosine and tryptophan metabolism are present in these primary headaches and, if so, their possible role in the chronicity process of CM and CTTH. The results show that important abnormalities of tyrosine metabolism are present only in CM patients (very high plasma levels of DA, NE and tryptamine). Tryptamine plasma levels were found significantly lower in both CM and CTTH patients. In view of this, we propose that migraine and, possibly, CH attacks derive from neurotransmitter and neuromodulator metabolic abnormalities in a hyperexcitable and hypoenergetic brain that spread from the frontal lobe, downstream, resulting in abnormally activated nuclei of the pain matrix. The low tryptamine plasma levels found in CM and CTTH patients suggest that these two primary chronic headaches are characterized by a common insufficient serotoninergic control of the pain threshold.

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“…It has been demonstrated that CSD is completely blocked by competitive and noncompetitive NMDA antagonists (Van Harreveld, 1984;Mody et aI., 1987;Goroleva et aI., 1987;Hansen et aI., 1988;Lauritzen et al, 1988;Marrannes et al, 1988). Therefore, if hypoglycemic depolarization and CSD were triggered by the same mechanism, we would expect some degree of blockage of the persistent depolarization in severe hypoglycemia in response to NMDA antagonism.…”

Section: Discussionmentioning

confidence: 94%

Influence of MK-801 on Brain Extracellular Calcium and Potassium Activities in Severe Hypoglycemia

Zhang

Hansen

Wieloch

et al. 1990

J Cereb Blood Flow Metab

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Summary:The purpose of the present study was to ex amine the effect of blockade of N-methyl-o-aspartate (NMDA) receptors on the depolarization associated with severe hypoglycemia, which is commonly preceded by one or a few transient depolarizations reminiscent of cor tical spreading depression (CSD). In the cerebral cortices of rats [K + le and [Ca2 + le were measured with ion selective microelectrodes. NMDA blockade was achieved by injection of MKSOI in doses that block CSD. In control rats, the latency from the time point when blood glucose reached minimal levels to onset of ionic shifts was 33.2 ± 3.5 min, and [K +le rose from 3.2 ± 0.2 to 55 ± 5 mM. All variables remained unchanged in ratsThe aim of the present study was to examine the mechanism of change of extracellular ionic activi ties associated with severe hypoglycemia (Astrup and Norberg 1976; Harris et aI., 1984). Previous studies have shown that the tissue concentrations of labile phosphates and energy charge remain con stant immediately preceding the large cortical changes of [K+]e and [Ca 2 +]e (Harris et aI., 1984). Therefore, the triggering of hypoglycemic depolar ization is not explained simply by a decline of en ergy metabolism.After onset of depolarization, the level of cortical ATP and phosphocreatine (PCr) decrease rapidly,

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The nature of the chick's magnesium‐sensitive retinal spreading depression

Cited by 51 publications

References 23 publications

Reentrant spiral waves of spreading depression cause macular degeneration in hypoglycemic chicken retina

Reentrant spiral waves of spreading depression cause macular degeneration in hypoglycemic chicken retina

Biochemistry of primary headaches: role of tyrosine and tryptophan metabolism

Influence of MK-801 on Brain Extracellular Calcium and Potassium Activities in Severe Hypoglycemia

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