低血糖后葡萄糖再灌注大鼠海马Nogo-A蛋白的表达

目的探讨胰岛素诱导大鼠低血糖后葡萄糖再灌注对大鼠海马Nogo-A蛋白表达的影响。方法41只4个月龄雄性Wistar大鼠随机分为3组:假手术组(Sham)、低血糖组(HG)、低血糖后葡萄糖再灌注组(HG/GR)。采用DAPI染色观察大鼠海马神经元的凋亡、坏死变化;免疫组织化学染色和Western免疫印迹检测大鼠海马Nogo-A蛋白的表达变化。结果①Nogo-A免疫组化染色:Nogo-A表达量Sham大于HG和HG/GR,三组之间比较,P<0.05;②Western免疫印迹:Nogo-A的表达量,Sham最大,HG次之,HG/GR最小,三组之间差异有统计学意义P<0.01,HG和HG/GR两组之间比较差异无统计学意义(P>0.05)。结论低血糖后再灌注葡萄糖,大鼠海马神经元坏死及凋亡程度增加,Nogo-A蛋白表达降低。     

新生儿低血糖脑损伤高危因素分析

目的 探讨新生儿低血糖脑损伤的高危因素及其对预后的影响.方法 回顾性分析2015年1 月至2018 年12 月贵州医科大学附属医院新生儿科收治的235 例新生儿低血糖患儿的临床资料,根据是否发生脑损伤分为脑损伤组和无脑损伤组,比较两组患儿的基本情况、母孕期及新生儿疾病情况、血糖相关资料,经SPSS 24.0统计软件处理...     

Effects of hypoglycemia on functional magnetic resonance imaging response to median nerve stimulation in the rat brain.

The authors studied the effects of a standardized mild-moderate hypoglycemic stimulus (glucose clamp) on brain functional magnetic resonance imaging (fMRI) responses to median nerve stimulation in anesthetized rats. In the baseline period (plasma glucose 6.6 +/- 0.3 mmol/L), the MR signal changes induced by median nerve activation were determined within a fixed region of the somatosensory cortex from preinfusion activation maps. Subsequently, insulin and a variable glucose infusion were administered to decrease plasma glucose. The goal was to produce a stable hypoglycemic plateau (2.8 +/- 0.2 mmol/L) for 30 minutes. Thereafter, plasma glucose was restored to euglycemic levels (6.0 +/- 0.3 mmol/L). In the early phase of insulin infusion (15 to 30 minutes), before hypoglycemia was reached (4.7 +/- 0.3 mmol/L), the activation signal was unchanged. However, once the hypoglycemic plateau was achieved, the activation signal was significantly decreased to 57 +/- 6% of the preinfusion value. Control regions in the brain that were not activated showed no significant changes in MR signal intensity. Upon return to euglycemia, the activation signal change increased to within 10% of the original level. No significant activation changes were noted during euglycemic hyperinsulinemic clamp experiments. The authors concluded that fMRI can detect alterations in cerebral function because of insulin-induced hypoglycemia. The signal changes observed in fMRI activation experiments were sensitive to blood glucose levels and might reflect increases in brain metabolism that are limited by substrate deprivation during hypoglycemia.     

Prevention of hypoglycemia-induced neuronal death by hypothermia

Hypothermia reduces neuronal damage after cerebral ischemia and traumatic brain injury, while hyperthermia exacerbates damage from these insults. Previously we have shown that temperature-dependent modulation of excitotoxic neuronal death is mediated in part by temperature-dependent changes in the synaptic release/translocation of Zn²⁺. In this study, we hypothesize that brain temperature also affects hypoglycemia-induced neuronal death by modulation of vesicular Zn²⁺ release from presynaptic terminals. To test our hypothesis, we used a rat model of insulin-induced hypoglycemia. Here we found that hypoglycemia-induced neuronal injury was significantly affected by brain temperature, that is, hypothermia inhibited while hyperthermia aggravated neuronal death. To investigate the mechanism of temperature-dependent neuronal death after hypoglycemia, we measured zinc release/translocation, reactive oxygen species (ROS) production, and microglia activation. Here we found that hypoglycemia-induced Zn²⁺ release/translocation, ROS production, and microglia activation were inhibited by hypothermia but aggravated by hyperthermia. Even when the insult was accompanied by hyperthermic conditions, zinc chelation inhibited ROS production and microglia activation. Zinc chelation during hyperthermia reduced neuronal death, superoxide production, and microglia activation, which was comparable to the protective effects of hypothermia. We conclude that neuronal death after hypoglycemia is temperature-dependent and is mediated by increased Zn²⁺ release, superoxide production, and microglia activation.     

Cerebral mitochondrial respiration in diabetic and chronically hypoglycemic rats

The respiratory function of cerebral mitochondria harvested from genetically diabetic (BB/W) and streptozotocin-diabetic rats deprived of insulin for 3-4 weeks was found to be unchanged from control values. Furthermore, insulin-deprived BB/W rats subjected to 30 min of insulin-induced hypoglycemic coma demonstrated a normal mitochondrial respiration following a 60 min period of glucose restitution, a finding consistent with earlier results in non-diabetic rats. However, in rats exposed to 1 week of moderate hypoglycemia (plasma glucose = 3.0 mumol.ml-1), both state 3 respiration and the respiratory control ratio (RCR) were reduced from control. In fact, when the chronic hypoglycemia was imposed following a 3-4 week period of diabetic hyperglycemia, the state 3 rate and RCR were found to be reduced to a greater degree than in chronically hypoglycemic, non-diabetic, previously normoglycemic rats. Finally, when 1 week of moderate hypoglycemia preceded a 30 min period of insulin-induced hypoglycemic coma, a disturbed pattern of mitochondrial respiration (i.e. increased state 4, decreased RCR) was found at 60 min of recovery following coma. These results indicate that chronic increases in glucose (and insulin deprivation) have no effect on cerebral mitochondrial respiratory function, whereas prolonged, albeit moderate, reductions in cerebral glucose supply result in perturbations in mitochondrial respiration. These results demonstrate the importance of an adequate glucose supply for normal mitochondrial activity.     

Brain injury from marked hypoxia in cats: role of hypotension and hyperglycemia

The present study identifies several factors that govern brain pathologic response to marked hypoxia. None of 13 cats exposed to 25 minutes of marked hypoxia (FiO2 = 3.4%; PaO2 = 17 +/- 3 mm Hg, S.D.) that maintained mean arterial blood pressure (MABP) greater than 65 mm Hg were brain injured after reoxygenation and long term survival. In contrast, 12 of 13 exposed to the same hypoxia but that experienced reductions in MABP less than 45 mm Hg for 4 +/- 1 minutes developed a pattern of brain injury closely resembling that of humans surviving in a persistent vegetative state after cardiorespiratory arrest. Higher serum glucose and lactate concentrations and lower blood pH values significantly correlated with development of hypotension during hypoxia. Four of 8 cats exposed to 21 minutes of marked hypoxia followed by 4 minutes of 100% N2 breathing that also led to hypotension similarly developed brain injury. Among the hypoxic/hypotensive cats the magnitude of the hyperglycemic response to hypoxia as modulated by 0, 1, or 2 days of preexposure fasting, strongly correlated with occurrence and extent of brain damage. Peak cisterna magna CSF lactate concentrations 10 to 30 minutes into recovery distinguished those animals that remained brain-intact (less than 13 mM) from those that developed brain damage (greater than 15 mM) with 100% accuracy. Seven cats developed delayed cardiogenic shock 3 to 12 hours into the recovery period. This outcome was predicted by blood pH values less than 6.70 shortly after resuscitation while all 27 surviving cats exhibited values greater than 6.80.     

Hypotension as a complication of hypoglycemia leads to enhanced energy failure but no increase in neuronal necrosis

The hypothesis that arterial hypotension aggravates hypoglycemic brain damage was tested. Thirty minutes of insulin induced hypoglycemia with a flat EEG ("isoelectricity") was compared in seven series of rats. In three series of animals, the energy state of the cerebral cortex was determined at blood pressures of 140, 100 and 80 mm Hg respectively. Hypotension during hypoglycemia exacerbated cortical energy failure. In the fourth to sixth series, blood pressure was adjusted during isoelectricity to 160, 100 and 60 mm Hg, respectively. A seventh series had induced hypotension to 60 mm Hg only in the recovery period. Quantitation of neuronal death was performed in the fourth to seventh series of rats by direct visual counting of acidophilic neurons in sub-serially sectioned brains after one week survival. Although the first three series demonstrated enhanced deterioration of the cerebral energy state with lower blood pressures during hypoglycemia, the fourth to seventh series showed no augmentation of quantitated hypoglycemic neuronal necrosis. The distinct distribution of hypoglycemic brain damage, suggesting a fluid-borne toxin, was present at normal and reduced blood pressures, with no tendency toward an ischemic pattern of pathology. In spite of previously demonstrated reductions of cerebral blood flow to ischemic levels in regions with pronounced loss of autoregulation, no regional exacerbation of neuronal necrosis was seen in these brain areas. It is concluded that hypoglycemic brain damage is distinct from ischemic brain damage, and that the two insults are not additive. Furthermore, moderate hypotension to 60 mm Hg does not aggravate the damage in spite of an enhanced energy failure.     

Hyperglycemic brain injury in the rat

Children with diabetes onset before 5 years of age have reduced neurocognitive function. This problem has been attributed to hypoglycemia, a complication of insulin therapy. The eye, kidney, and nerve complications of diabetes (hyperglycemia) have been reduced by intensified insulin therapy which is associated with a 3-fold increase in severe hypoglycemia and therefore is not recommended for children less than 13 years of age. Since hyperglycemia is much more common than intermittent hypoglycemia during early childhood diabetes, it is important to determine if hyperglycemia affects brain growth and development. Rats were exposed to 4 weeks of either continuous hyperglycemia (diabetes) or intermittent (3 h, 3 times/week) hypoglycemia from 4 to 8 weeks of age. The brains of these animals were compared to those of similarly aged normal control animals. The cell number was increased, and the cell size reduced in the cortex of diabetic animals as assessed by DNA/wet weight of brain and protein/DNA content. Reduced amounts of protein, fatty acids, and cholesterol/microgram DNA also indicate smaller cells with reduced myelin content in the cortex of the diabetic animals. Histologic evaluation of these brains confirmed the biochemical findings. These observations require further confirmation and evaluation but indicate that continuous hyperglycemia may be more damaging than intermittent hypoglycemia to the developing brain. This is an important consideration for the management of diabetes mellitus in young children.     

Processing of food stimuli is selectively enhanced during insulin-induced hypoglycemia in healthy men

Recently it has been reported that during insulin-induced hypoglycemia selective attention is directed to food stimuli suggesting an adaptive cognitive strategy to escape from this potentially dangerous metabolic state. Here, we tested this hypothesis using a short-term memory task. We also aimed to define a hypoglycemic threshold level at which such an adaptive cognitive strategy first occurs. Fifteen healthy men underwent stepwise hypoglycemic (plasma glucose: 4.1-3.6-3.1-2.6 mmol/l) and euglycemic clamp experiments. Clamps were performed in a single blind fashion within a cross-over design with the order balanced across subjects. During the clamps cognitive function tests (short-term recall of food-related and non-food-related words; Stroop task) were applied at baseline and each hypoglycemic plateau, and at the corresponding time intervals of the euglycemic clamp. Performance on all cognitive function tests applied deteriorated during the hypoglycemic as compared to the euglcemic clamp (all P<0.02). Separate analyses at each hypoglycemic plateau revealed that food and non-food related short-term memory was similar during baseline and mild hypoglycemia. However, at the hypoglycemic target level of 2.6 mmol/l recall of food related words was higher than non-food related words when compared to the euglycemic control clamp condition (p=0.024). Performance on the word-color conflict Stroop task became significantly impaired first at the lowest hypoglycemic plateau (2.6 mmol/l), while performance on the Stroop subtests 'color naming' and 'word reading' were already impaired at higher plasma glucose levels (3.6 and 3.1 mmol/l; respectively). Collectively, data of the Stroop task indicate that the control of attention via executive mechanisms is less sensitive to insulin-induced hypoglycemia than pre-attentive automated stimulus processing (reading, naming). If executive control of attention becomes affected by hypoglycemia, cognitive resources appear to be preferentially allocated to the processing of food stimuli.     

Hypoglycemia reduces the blood-oxygenation level dependent signal in primary auditory and visual cortex: a functional magnetic resonance imaging study

Studies of the effects of hypoglycemia on the brain using neurocognitive testing have suggested that mainly complex functions subserved by secondary and tertiary cortex are affected by mild to moderate hypoglycemia and that intensively treated patients with Type I diabetes mellitus (T1DM) may have altered sensitivity to the central nervous system effects of hypoglycemia. Functional magnetic resonance imaging provides a sensitive, regionally-specific probe of possible neurophysiologic changes related to hypoglycemia in the brain. Eleven intensively-treated T1DM patients and 11 matched non-diabetic controls took part in a 2-day protocol in which functional magnetic resonance imaging (MRI) was used to measure changes in the patterns of brain activation produced by simple auditory and visual stimuli in different conditions. On one day, participants were euglycemic the entire time. On the other day, an initial 50-min euglycemic period was followed by a 50-min hypoglycemic period. Results indicated that hypoglycemia reduced the amplitude of the blood-oxygenation level dependent response in primary auditory and visual cortex to simple auditory and visual stimuli. The latency and duration of the transient hemodynamic response function were not affected. Responses to hypoglycemia were similar in diabetic and non-diabetic participants. These results suggest that mild to moderate hypoglycemia may alter the balance of blood flow and oxygen extraction when glucose levels are lowered. Intensively-treated T1DM, with its attendant frequent hypoglycemic episodes, did not seem to alter hypoglycemic responses in primary visual and auditory cortex.     

microRNA-455-5p alleviates neuroinflammation in cerebral ischemia/reperfusion injury

Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion.Downregulation of microRNA(miR)-455-5p after ischemic stroke has been considered a potential biomarker and therapeutic target for neuronal injury after ischemia.However,the role of miR-455-5p in the post-ischemia/reperfusion inflammatory response and the underlying mechanism have not been evaluated.In this study,mouse models of cerebral ischemia/reperfusion injury were established by transient occlusion of the middle cerebral artery for 1 hour followed by reperfusion.Agomir-455-5p,antagomir-455-5p,and their negative controls were injected intracerebroventricularly 2 hours before or 0 and 1 hour after middle cerebral artery occlusion(MCAO).The results showed that cerebral ischemia/reperfusion decreased miR-455-5p expression in the brain tissue and the peripheral blood.Agomir-455-5p pretreatment increased miR-455-5p expression in the brain tissue,reduced the cerebral infarct volume,and improved neurological function.Furthermore,primary cultured microglia were exposed to oxygen-glucose deprivation for 3 hours followed by 21 hours of reoxygenation to mimic cerebral ischemia/reperfusion.miR-455-5p reduced C-C chemokine receptor type 5 mRNA and protein levels,inhibited microglia activation,and reduced the production of the inflammatory factors tumor necrosis factor-αand interleukin-1β.These results suggest that miR-455-5p is a potential biomarker and therapeutic target for the treatment of cerebral ischemia/reperfusion injury and that it alleviates cerebral ischemia/reperfusion injury by inhibiting C-C chemokine receptor type 5 expression and reducing the neuroinflammatory response.     

Macrophage colony-stimulating factor is expressed in neuron and microglia after focal brain injury.

In a previous study, we have demonstrated that damaged neurons within a boundary area around necrosis fall into delayed neuronal death owing to the cytotoxic effect of microglial nitric oxide (NO), and these neurons are finally eliminated by activated microglia. In this process, microglia are activated to release NO, increase in number, and accumulate toward the damaged area. In this study, we investigated the expression of macrophage colony-stimulating factor (M-CSF, also called colony stimulating factor-1; CSF-1) and other cytokines, which are reported to relate to activation, proliferation, or migration of microglia. The mRNA of M-CSF arose biphasically from 30 min to 1 hr and from 6 to 72 hr after the injury, as demonstrated by semiquantitative RT-PCR. However, another cytokine of granulocyte-macrophage CSF (GM-CSF) or interleukin-3 (IL-3), which causes proliferation of microglia in vitro, was not detected. From immunohistochemical studies, positive staining of M-CSF was observed mainly in neuron-specific enolase (NSE)-positive cells from 1 to 12 hr after the injury, and after that M-CSF became positive in Griffonia simplicifolia isolectin-B4 (GSA-I-B4)-positive cells from 24 to 72 hr in the boundary area around necrosis. These results suggest that neurons around the damaged area express M-CSF in the early phase after injury, which may initially activate microglia, and these activated microglia also express M-CSF later, causing further proliferation or migration of microglia themselves to eliminate damaged neurons or necrotic brain tissue.     

The dentate gyrus in hypoglycemia: Pathology implicating excititoxin-mediated neuronal necrosis

Summary A detailed light- and electron-microscopic study of the damage to the rat dentate gyrus in hypoglycemia was undertaken, in view of the previously advanced hypothesis that hypoglycemic nerve cell injury is mediated by a released neurotoxin. The distribution of neuronal necrosis showed a relationship to the subarachnoid cisterns.Electron microscopy of the dentate granule cells and their apical dendrites revealed dendrosomal, axon-sparing neuronal pathology. Dentate granule cells were affected first in the dendrites in the outer layer of the stratum moleculare, sparing axons of passage and terminal boutons. Subsequently, the neuronal perikarya were affected, and Wallerian degeneration of axons followed. Cell membrane abnormalities preceded the appearance of mitochondrial flocculent densities and degradation of the cytoskeleton, and are suggested to be early lethal changes.The observed early dendrotoxic changes, and the dendrosomal, axon-sparing nature of the lesion implicate an excitotoxin-mediated neuronal necrosis in hypoglycemia.Supported by the Swedish Medical Research Council (projects 12X-03020, 12X-07123, 14X-263), the Finnish Medical Research Council, and the National Institutes of Health of the United State Public Health Service (grant no. 5 RO1 NS07838)     

Chronic hyperglycemic diabetes in the rat is associated with a selective impairment of cerebral vasodilatory responses

Diabetes has been reported to impair vasodilatory responses in the peripheral vascular tissue. However, little is known about vasodilatory function in the diabetic brain. We therefore studied, in the N2O-sedated, paralyzed, and artificially ventilated rat, the effects of chronic hyperglycemic diabetes on the cerebral blood flow (CBF) responses to 3 acutely imposed vasodilatory stimuli: hypoglycemia (HG) (plasma glucose = 1.6-1.9 mumol ml-1), hypoxia (HX) (PaO2 = 35-38 mm Hg), or hypercarbia HC) (PaCO2 = 75-78 mm Hg). In addition, we evaluated the somatosensory evoked potential (SSEP) and plasma catecholamine changes in rats exposed to acute glycemic reductions. Diabetes was induced via streptozotocin (STZ, 60 mg kg-1 i.p.). All results in diabetic rats were compared to those obtained in age-matched nondiabetic controls. The animals were studied at 6-8 weeks (HG experiments) or 4-6 months (HG, HX, and HC experiments) post-STZ. Values for CBF were obtained for the cortex (CX), subcortex (SC), brainstem (BS), and cerebellum (CE) employing radiolabeled microspheres. Up to three CBF determinations were made in each animal. In 6-8 week diabetics vs. controls, CBF increased to a lesser value in the CX, SC, and BS (p less than 0.05). Thus, in the diabetics, going from chronic hyperglycemia to acute hypoglycemia, CBF values (in ml 100 g-1 min-1 +/- SD) increased (p less than 0.05) from 89 +/- 22 to 221 +/- 57 in the CX, from 82 +/- 21 to 160 +/- 52 in the SC, and from 79 +/- 34 to 237 +/- 125 in the BS. In controls, going from normoglycemia to acute hypoglycemia, the CBF changes (p less than 0.05) were 128 +/- 27 to 350 +/- 219 (CX), 117 +/- 11 to 358 +/- 206 (SC), and 130 +/- 29 to 452 +/- 254 (BS). CBF changes and absolute values in the CE were similar in the two groups. At 4-6 months post-STZ, a complete loss of the hypoglycemic CBF response was found in the CX, SC, and CE. In the BS, a CBF response to hypoglycemia was seen in the diabetic rats, with the CBF increasing from 114 +/- 28 (hyperglycemia) to 270 +/- 204 ml 100 g-1 min-1 (p less than 0.05), compared to a change from 147 +/- 36 (normoglycemia) to 455 +/- 299 ml 100 g-1 min-1 (p less than 0.05) in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

L-carnitine inhibits hypoglycemia-induced brain damage in the rat

Hypoglycemia sometimes occurs in patients with diabetes mellitus who receive excessive doses of insulin. Severe hypoglycemia has been known to induce mitochondrial swelling followed by neuronal death in the brain. Since L-carnitine effectively preserves mitochondrial function in various cells both in vitro and in vivo, we investigated its effects on the neuronal damage induced by hypoglycemic insult in male Wistar rats. Animals were given L-carnitine-containing water (0.1%) for 1 week and then received insulin (20 U/kg, i.p.) to induce hypoglycemia. Although L-carnitine did not affect the mortality of animals that developed hypoglycemic shock, it improved the cognitive function of the survived animals as assessed by the Morris water-maze test. L-carnitine effectively inhibited the increase in oxidized glutathione and mitochondrial dysfunction in the hippocampus and prevented neuronal injury. L-carnitine also inhibited the decrease in mitochondrial membrane potential and the generation of reactive oxygen species in hippocampal neuronal cells cultured in glucose-deprived medium. These results suggest that L-carnitine prevents hypoglycemia-induced neuronal damage in the hippocampus, presumably by preserving mitochondrial functions. Thus, L-carnitine may have therapeutic potential in patients with hypoglycemia induced by insulin overdose.     

Effects of fasting and insulin-induced hypoglycemia on brain cell membrane function and energy metabolism during hypoxia-ischemia in newborn piglets.

This study was done to determine the effects of 12 h fasting-induced mild hypoglycemia (blood glucose 60 mg/dl) and insulin-induced moderate hypoglycemia (blood glucose 35 mg/dl) on brain cell membrane function and energy metabolism during hypoxia-ischemia in newborn piglets. Sixty-three ventilated piglets were divided into six groups; normoglycemic control (NC, n=8), fasting-induced mildly hypoglycemic control (FC, n=10), insulin-induced moderately hypoglycemic control (IC, n=10), normoglycemic/hypoxic-ischemic (NH, n=11), fasting-induced mildly hypoglycemic/hypoxic-ischemic (FH, n=12) and insulin-induced moderately hypoglycemic/hypoxic-ischemic (IH, n=12) group. Cerebral hypoxia-ischemia was induced by occlusion of bilateral common carotid arteries and simultaneous breathing with 8% oxygen for 30 min. The brain lactate level was elevated in NH group and this change was attenuated in FH and IH groups. The extent of cerebral lactic acidosis during hypoxic-ischemic insult showed significant positive correlation with blood glucose level (r=0.55, p<0.001). Cerebral Na+, K+-ATPase activity and concentrations of high-energy phosphate compounds were reduced in NH group and these changes were not ameliorated in FH or IH group. Cortical levels of conjugated dienes, measured as an index of lipid peroxidation of brain cell membrane, were significantly elevated in NH, FH and IH groups compared with NC, FC and IC groups and these increases were more profound in FH and IH with respect to NH. Blood glucose concentration showed significant inverse correlation with levels of conjugated dienes (r=-0.35, p<0.05). These findings suggest that, unlike in adults, mild or moderate hypoglycemia, regardless of methods of induction such as fasting or insulin-induced, during cerebral hypoxia-ischemia is not beneficial and may even be harmful in neonates.     

Insulinoma: reversal of brain magnetic resonance imaging changes following resection

Insulinoma presents with myriad manifestations and severe neurological deficit may develop due to delay in diagnosis. We report a lady who presented with Glasgow coma scale of E1 M2 V1, which did not improve after correction of hypoglycemia. There was complete reversal of neurological deficit and brain magnetic resonance imaging changes of hypoglycemia on follow-up after resection of pancreatic insulinoma. This is the first report which shows reversal of hypoglycemic changes in MRI after resection of insulinoma. Insulinoma, pre and post surgery provides a model for study of the effect of hypoglycemia and its improvement after euglycemia.     

Changing pattern of perinatal brain injury in term infants in recent years

Perinatal brain injury in term infants remains a significant clinical problem. Recently a change appears to have occurred in the pattern of such injuries. We sought to characterize the incidence, etiology, clinical manifestations, and outcomes of these injuries. A retrospective chart review identified clinical characteristics of neuroimaging, electroencephalography, and placental pathologic findings. Perinatal depression was defined as hypotonia and the need for respiratory support. From January 2004-December 2009, 29,597 term deliveries occurred. Brain injuries in 33 infants (live term births) included hypoxic-ischemic encephalopathy (n = 8; 0.27/1000), subdural hemorrhage (n = 10; 0.34/1000), intraventricular/intraparenchymal hemorrhage (n = 5; 0.17/1000), and focal cerebral infarctions (n = 4; 0.14/1000). Thirteen of 33 infants (39%) were triaged to a regular nursery. Delayed presentations included apnea (n = 6), desaturation episodes (n = 3), and seizures (n = 4). Twenty of 33 (61%) were admitted directly to the neonatal intensive care unit because of perinatal depression or evolving hypoxic-ischemic encephalopathy. Clinical signs included seizures (n = 12) and apnea (n = 2). Nine of 19 manifested electroencephalographic seizures. Pathology included chorioamnionitis (n = 7) and fetal thrombotic vasculopathy (n = 5). The latter was associated with focal cerebral infarctions in 3/4 cases. Most cases attributable to perinatal brain injury, except for evolving hypoxic-ischemic encephalopathy, are not identified according to any perinatal characteristics until the onset of signs, limiting opportunities for prevention.