Neurologic Deficit and Cerebral ATP Depletion after Temporary Focal Ischemia in Cats

Abstract

Summary: Focal ischemia was induced in 23 cats by oc cluding the left middle cerebral artery for 2 h. The animals were then divided into groups for unforced reperfusion of variable duration ranging from 2 to 48 h. Neurological ratings were obtained during both ischemia and reperfu sion. Following planned sacrifice the regional ATP con tent was assessed by means of a bioluminescence method showing spatial distribution and degree of ATP depletion. All the animals developed a neurologic deficit, with a median of 6 points on a disability scale of 0-10. After reopening of the middle cerebral artery, neurologic re covery was quite variable depending on the initial neu rologic deficit (partial <P = 0. 6 7, PI < 0.05): Animals with In prolonged experiments involving permanent occlusion of the middle cerebral artery (MeA) in cats a relationship between the temporal pattern of flow changes and the degree of neurological re covery has been established (Heiss et al., 1976). The outcome was best when spontaneous reperfu sion of the MeA region reached a sufficient level within 4 h after the onset of ischemia. Spontaneous hyperperfusion developing within 2-4 h in the pre viously ischemic region, as well as hyporeperfusion at flow values continuously below 40% of control values, usually resulted in gross infarcts and a fatal outcome within the first few days. After complete temporary cerebral ischemia, at least partial nor malization of the cerebral metabolism and electro physiologic activity was observed (Hossmann and Kleihues, 1973;Hossmann and Zimmermann, 1974; Dr. Sato's present address is Department of Neurosurgery, Osaka University Hospital, 1-1-50 Fukushima, Fukushima Osaka 553, Japan. Nordstrom et aI., 1978), but recovery of neurolog ical function was not described. The present study was designed to investigate the effect of reperfu sion, after temporary MeA occlusion, on neurolog ical recovery in relation to persistent metabolic de fects as demonstrated by regional ATP depletion in brain slices. METHODS Preparation of animalsTwenty-three cats of either sex weighing 2.0-3.

Pial arterial pressure in cats following middle cerebral artery occlusion. II. Relationship to regional disturbance of energy metabolism.

“…This is in accordance with recent observations that 120 min reversible MCA occlusion in cats leads to irreversible damage of the energyproducing metabolism. 18 The sequence of glycolytic changes following occlusion of a main supplying brain artery are well- This pattern of substrates is obtained following shortterm MCA occlusion in cats. 8 In contrast, in the present series of experiments only a small part of the tissue depleted of ATP exhibited increased NADH-fluorescence after 120 min MCA occlusion, and in about 50% of animals there was a decreased NADH-fluorescence in regions with a disturbed metabolism.…”

Neurological deficit and cerebral infarction after temporary middle cerebral artery occlusion in unanesthetized cats.

“…Studies of the cortical distribution of local CBF reduction and metabolic impairment and correlation with histological damage after MCA occlusion in cats have been reported, but the relation to postischemic neurological function and the effect of reperfusion was not evaluated in most of these experiments. 12 ' 14~17 In our study, the slight improvement of one grade or less during 4-8-hr temporary occlusions in two cats suggests that collateral blood flow may have improved spontaneously before the occluder was released. ' 8 The variable neurological and pathologic responses in each group may also be explained by differences in initial collateral flow patterns.…”

“…l3 Studies of blood flow restoration after regional cerebral ischemia is induced by temporary clipping of the middle cerebral artery (MCA) in cats and monkeys have shown that the mortality rate is lower, the neurological deficit less severe, and infarct size smaller after 6-hr occlusion than after permanent ligation, despite the occurrence of hyperemia and edema following reperfusion, 12 Those experiments, however, were done immediately after surgical exposure of the MCA in anesthetized animals. General anesthesia and controlled ventilation might have had a protective effect, and ischemia might have been aggravated by vasospasm after vascular dissection and clipping.…”

Peripheral Nervous System

“…Neurological deficit and ATP depletion occurs after focal ischaemia (Sato et al 1984). During brain ischaemia, tissue stores of ATP are depleted and released ATP is rapidly degraded to adenosine with subsequent release of excitotoxic amino acids leading to ischaemic damage (Phillis et al 1991).…”