Experimental Imaging Study of Encephalomalacia Fluid-Attenuated Inversion Recovery (FLAIR) Hyperintense Lesions in Posttraumatic Epilepsy.

This study introduced new MRI techniques such as neurite orientation dispersion and density imaging (NODDI); NODDI applies a three-compartment tissue model to multishell DWI data that allows the examination of both the intra- and extracellular properties of white matter tissue. This, in turn, enables us to distinguish the two key aspects of axonal pathology-the packing density of axons in the white matter and the spatial organization of axons (orientation dispersion (OD)). NODDI is used to detect possible abnormalities of posttraumatic encephalomalacia fluid-attenuated inversion recovery (FLAIR) hyperintense lesions in neurite density and dispersion. Methods. 26 epilepsy patients associated with FLAIR hyperintensity around the trauma encephalomalacia region were in the epilepsy group. 18 posttraumatic patients with a FLAIR hyperintense encephalomalacia region were in the nonepilepsy group. Neurite density and dispersion affection in FLAIR hyperintense lesions around encephalomalacia were measured by NODDI using intracellular volume fraction (ICVF), and we compare these findings with conventional diffusion MRI parameters, namely, fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Differences were compared between the epilepsy and nonepilepsy groups, as well as in the FLAIR hyperintense part and in the FLAIR hypointense part to try to find neurite density and dispersion differences in these parts. Results. ICVF of FLAIR hyperintense lesions in the epilepsy group was significantly higher than that in the nonepilepsy group (P < 0.001). ICVF reveals more information of FLAIR(+) and FLAIR(-) parts of encephalomalacia than OD and FA and ADC. Conclusion. The FLAIR hyperintense part around encephalomalacia in the epilepsy group showed higher ICVF, indicating that this part may have more neurite density and dispersion and may be contributing to epilepsy. NODDI indicated high neurite density with the intensity of myelin in the FLAIR hyperintense lesion. Therefore, NODDI likely shows that neurite density may be a more sensitive marker of pathology than FA.

Biofuels Co-Products Tolerance and Toxicology for Ruminants: An Update.

Corn co-products are a co-product of the dry and wet corn-milling ethanol manufacturing industry. The dry mill corn co-product is distiller's grains. Distillers grain can be further categorized into dry distillers grains (DDG), DDG with solubles, wet distillers grains with solubles (WDGS), modified WDGS, and corn syrup (solubles). Wet mill ethanol production produces 2 main feed stuffs: corn gluten (wet and dry) and heavy steep water.

The Relation of Focal Lesions to Cortical Thickness in Pediatric Traumatic Brain Injury.

In a sample of children with traumatic brain injury, this magnetic resonance imaging (MRI)-based investigation examined whether presence of a focal lesion uniquely influenced cortical thickness in any brain region. Specifically, the study explored the relation of cortical thickness to injury severity as measured by Glasgow Coma Scale score and length of stay, along with presence of encephalomalacia, focal white matter lesions or presence of hemosiderin deposition as a marker of shear injury. For comparison, a group of children without head injury but with orthopedic injury of similar age and sex were also examined. Both traumatic brain injury and orthopedic injury children had normally reduced cortical thickness with age, assumed to reflect neuronal pruning. However, the reductions observed within the traumatic brain injury sample were similar to those in the orthopedic injury group, suggesting that in this sample traumatic brain injury, per se, did not uniquely alter cortical thickness in any brain region at the group level. Injury severity in terms of Glasgow Coma Scale or longer length of stay was associated with greater reductions in frontal and occipitoparietal cortical thickness. However, presence of focal lesions were not related to unique changes in cortical thickness despite having a prominent distribution of lesions within frontotemporal regions among children with traumatic brain injury. Because focal lesions were highly heterogeneous, their association with cortical thickness and development appeared to be idiosyncratic, and not associated with group level effects.

Assessment of ruminal hydrogen sulfide or urine thiosulfate as diagnostic tools for sulfur induced polioencephalomalacia in cattle.

To determine if ruminal hydrogen sulfide, urine thiosulfate, or blood sulfhemoglobin could be used as diagnostic indicators for sulfur-induced polioencephalomalacia, 16 steers (8 cannulated, 368 ± 12 kg; 8 unmodified, 388 ± 10 kg; mean ± standard error) were fed 1 of 2 dietary treatments. Diets consisted of a low sulfate (0.24% S; control) wheat midd-based pellet or the control pellet with sodium sulfate added to achieve a high-sulfate (0.68% S) pellet. As designed, intake did not differ (P = 0.80) between treatments. At 8 hr postfeeding, ruminal hydrogen sulfide was not affected by cannulation (P = 0.35) but was greater (P < 0.01) in high S (6,005 ± 475 mg/l) than control (1,639 ± 472 mg/l) steers. Time of day of sampling affected (P = 0.01) ruminal hydrogen sulfide, with peak concentrations occurring 4-12 hr after feeding. Urine was collected prefeeding (AM) and 7-9 hr postfeeding (PM). Urine thiosulfate concentrations of high S steers sampled in the PM were greater (P > 0.01) than in the AM. However, there was no difference due to time of sampling for control. In both the AM and PM, urine thiosulfate concentrations of high S were greater (P > 0.01) than control. Although hydrogen sulfide and thiosulfate were elevated by increased dietary S intake, a concentration at which polioencephalomalacia is likely to occur could not be determined. Sampling urine for thiosulfate or rumen gas for hydrogen sulfide of nonsymptomatic pen mates 4-8 hr after feeding may be useful to assess sulfur exposure and differentiate between causes of polioencephalomalacia.

Intracerebral lipopolysaccharide induces neuroinflammatory change and augmented brain injury in growth-restricted neonatal rats.

INTRODUCTION: Intrauterine growth restriction (IUGR) alters fetal development and is associated with neurodevelopmental abnormalities. We hypothesized that growth restriction from reduced intrauterine perfusion would predispose neonatal rats to subsequent inflammatory brain injury. METHODS: In this study, IUGR was achieved by induced placental insufficiency in pregnant rats at 14 days of gestation. IUGR offspring and sham-operated control pups were subsequently injected with intracerebral lipopolysaccharide (LPS) as a model of periventricular leukomalacia (PVL). RESULTS: LPS similarly elevates proinflammatory cytokines in the brains of both IUGR and control rat pups. However, the chemokines cytokine-induced neutrophil chemoattractant-1 (CINC-1) and macrophage chemoattractant protein-1 (MCP-1), as well as microglia activation, were significantly higher in LPS-treated IUGR rat pups as compared with LPS-treated controls. In addition to the unique brain inflammatory response, IUGR rat pups demonstrated increased brain damage with an increased number of apoptotic cells, larger lateral ventricular size, and more severe impairment of myelination. DISCUSSION: This study provides evidence that placental insufficiency may sensitize the innate immune system in the immature brain and reveals a possible link between brain inflammation and injury.

ASAS Centennial Paper: contributions in the Journal of Animal Science to understanding cattle metabolic and digestive disorders.

Acute and subacute ruminal acidosis, bloat, liver abscesses, and polioencephalomalacia (PEM) were reviewed with respect to contributions published in the Journal of Animal Science (JAS) regarding these metabolic and digestive disorders in beef cattle. Increased grain feeding and expansion of the feedlot industry in the 1960s led to considerable research on acidosis, and early publications defined ruminal changes with acute acidosis. The concept of subacute acidosis was developed in the 1970s. Significant research was published during the 1980s and 1990s on adaptation to high-grain diets, effects of ionophores, and the development of model systems to study ruminal and metabolic changes in acidosis. Since 2000, JAS publications on acidosis have largely focused on individual animal variability in response to acid loads and the role of management strategies in controlling acidosis. Increased grain feeding also was associated with an increase in the incidence of liver abscesses, which were quickly linked to insults to the ruminal epithelium associated with acidosis. The role of antibiotics, particularly tylosin, in decreasing the incidence and severity of liver abscesses was a significant contribution of JAS publications during the 1970s and 1980s. Papers on bloat were among the earliest published in JAS related to metabolic and digestive disorders in cattle. Noteworthy accomplishments in bloat research chronicled in JAS include the nature of ruminal contents in legume and feedlot bloat, the role of plant fractions and microbial populations in the development of bloat, and the efficacy of poloxalene, ionophores, and, more recently, condensed tannins in decreasing the incidence and severity of bloat. Although less research has been published on PEM in JAS, early publications highlighting the association between PEM and ruminal acidity and the role of thiaminase in certain forms of the disorder, as well as more recent publications related to the role of sulfur in the development of PEM, are noteworthy contributions. Since the 1940s, outstanding and often-cited review articles have made JAS a highly visible source of information on these disorders. Thus, JAS has played a significant role as a repository for information pertaining to metabolic and digestive disorders in cattle and other ruminants, and it will no doubt continue to be a premier resource for information on these conditions during the second century of the American Society of Animal Science.

Brain, liver and plasma unsaturated aldehydes in nutritional encephalomalacia of chicks.

Vitamin E deficiency and linoleic acid-feeding lead to nutritional encephalomalacia (NE) in chicks, affecting the cerebellum exclusively. The relevance of lipid peroxidation (LPO) products to the pathogenesis of the disease was studied. Laying hens received a diet low in vitamin E. Resulting chicks were assigned to four groups fed either with linoleic (C18: 2n-6) or linolenic (C18: 3n-3) acid together with 1 or 50 p.p.m. vitamin E. Nine days post-hatching NE occurred in the vitamin E-deficient group fed linoleic acid. With each chick showing NE, a healthy one from all four groups was killed. Unsaturated aldehydes were determined in plasma, liver, cerebrum and cerebellum. Results underlined that the type of dietary fat is decisive for the aldehyde pattern. In the liver of linoleic acid-fed animals total aldehydes were increased. Diseased animals had increased aldehydes stemming from n-3 fatty acids. In plasma, vitamin E deficiency led to higher malondialdehyde and OH-nonenal concentrations. In brain, neither vitamin E deficiency nor NE were accompanied by increased aldehyde concentrations. In consequence a direct role of unsaturated aldehydes for the development of NE in the cerebellum is not probable.

Toxicology of Astragalus lusitanicus Lam.

Astragalus lusitanicus is a toxic legume grown in Morocco and in some other Mediterranean countries. In small ruminants, poisoning by this plant is dominated by nervous signs characterized by many cycles of excitement-depression. Macroscopic examination of poisoned animals showed congestive lesions and oedema in the brain and lungs. Microscopic lesions consisted mainly of vacuolar degeneration in neurons, hepatocytes and in spleen and kidney cells. Serum activity of AST and CK as well as blood glucose and urea were increased as a result of poisoning. However, serum activity of alpha-mannosidase was not modified as is the case in locoism. Chemical investigations showed that A. lusitanicus does not contain swainsonine or miserotoxin and its selenium concentration is very low. However, this legume contains indolizidin alkaloids and a first compound was purified and identified.

Repin-induced neurotoxicity in rodents.

Russian knapweed is a perennial weed found in many parts of the world, including southern California. Chronic ingestion of this plant by horses has been reported to cause equine nigropallidal encephalomalacia (ENE), which is associated with a movement disorder simulating Parkinson's disease (PD). Repin, a principal ingredient purified from Russian knapweed, is a sesquiterpene lactone containing an alpha-methylenebutyrolactone moiety and epoxides and is a highly reactive electrophile that can readily undergo conjugation with various biological nucleophiles, such as proteins, DNA, and glutathione (GSH). We show in this study that repin is highly toxic to C57BL/6J mice and Sprague-Dawley rats and acutely induces uncoordinated locomotion associated with postural tremors, hypothermia, and inability to respond to sonic and tactile stimuli. We also show that repin intoxication reduces striatal and hippocampal GSH and increases total striatal dopamine (DA) levels in mice. Striatal microdialysis in rats, however, has demonstrated a significant reduction of extracellular DA levels. These findings, coupled with the absence of any demonstrable change in striatal DOPAC levels, suggest that repin acts by inhibiting DA release, a hypothesis that is further supported by our demonstration that, in cultured PC12 cells, repin inhibits the release of DA without affecting its uptake. We believe, therefore, that inhibition of DA release represents one of the earliest pathogenetic events in ENE, leading eventually to striatal extracellular DA denervation, oxidative stress, and degeneration of nigrostriatal pathways. Since the neurotoxic effects of repin appear to be mediated via oxidative stress, and since repin is a natural product isolated from a plant in our environment that can cause a movement disorder associated with degeneration of nigrostriatal pathways, clarification of the mechanism of repin neurotoxicity may provide new insights into our understanding of the pathogenesis of PD.

Polioencephalomalacia.

Polioencephalomalacia (PEM) is a neuropathologic condition of ruminants that can be induced by a variety of neural metabolic disruptions. These include altered thiamine status, water deprivation-sodium ion toxicosis, lead poisoning, and high sulfur intake. Investigations of sulfur-related PEM have demonstrated that the onset of the clinical signs coincides with excessive ruminal sulfide production. A number of ruminal factors could modulate the production and absorption of ruminal sulfide. The development of a convenient method to estimate ruminal gas cap H2S has made it possible to identify cattle with high levels of ruminal H2S and evaluate their risk of developing PEM.

In vivo indicators of pathologic ruminal sulfide production in steers with diet-induced polioencephalomalacia.

Two groups of 3 120-160-kg Holstein steers were fed a diet high in carbohydrate and low in long fiber and either with or without added sodium sulfate. Prior to and during the course of feeding the experimental diet, the concentrations of rumen hydrogen sulfide gas and rumen fluid sulfide were determined by a simple sulfide detector tube method and by sulfide-selective electrode, respectively. Other measurements included rumen fluid pH, blood creatine kinase, and blood sulfhemoglobin. Two of the 3 steers fed the high-sulfate diet developed signs and lesions of polioencephalomalacia. Clinical signs included episodic ataxia and blunted or absent menace reaction. Increased ruminal H2S gas concentrations occurred in all 3 steers consuming the diet with added sulfate. The onset of clinical signs coincided with the onset of elevated H2S concentrations. These increases were 40-60 times the values measured in the steers consuming the diet without added sulfate. In contrast, increases in rumen fluid sulfide concentrations usually rose to 4 times that of control steers. The steers fed an identical diet but without added sulfate exhibited no signs or lesions of polioencephalomalacia and no elevations of sulfide in rumen gas or fluid. All steers had a modest decrease in rumen fluid pH associated with the transition to the concentrate diet. No significant changes were observed in any of the blood measurements of any of the steers. An additional pair of steers was fed the experimental diet with or without added sulfate to compare the ruminal H2S gas concentrations estimated by H2S detector tubes with those estimated by a different method of analysis utilizing charcoal trapping of H2S, conversion to sulfate, and measurement of the sulfate. Both methods yielded comparable estimates of H2S concentration. Overall, these data indicate that changes in rumen gas cap H2S concentrations are larger than changes in rumen fluid sulfide concentration and the estimation of rumen gas cap H2S concentration may be a practical approach to detecting pathologic increases in ruminal H2S gas. This simple, rapid, minimally invasive method should be useful for estimating the H2S content of ruminal gas under field conditions.

Phospholipid fatty acids of brain and liver are modified by alpha-tocopherol and dietary fat in growing chicks.

Dietary fatty acids modify phospholipid fatty acids in brain and liver of growing chickens post-hatching. The effect of vitamin E deficiency on this process is unknown and may be relevant to the pathogenesis of chick nutritional encephalomalacia (NE). Therefore laying hens received a diet low in vitamin E (10 mg alpha-tocopherol/kg feed). Resulting chicks were assigned to nine dietary groups each fed with either oleic (18:1n-9, 58 g/kg), linoleic (18:2n-6, 57 g/kg) or linolenic (18:3n-3, 56 g/kg) acid together with 5. 25 or 125 mg alpha-tocopherol/kg feed. NE affecting the cerebellum only occurred in the group given linoleic acid and 5 mg alpha-tocopherol/kg. In 1-d-old chicks and after 1 and 2 weeks the phospholipid fatty acid composition of liver, cerebrum and cerebellum (additionally after 3 weeks) was determined. The feed fatty acids were incorporated into the liver very efficiently during the first week of life. Unsaturation of liver membranes decreased in the order dietary linolenic > linoleic > oleic acid. In liver, also, the effect of alpha-tocopherol supplementation on phospholipid fatty acids was most pronounced. The unsaturation index increased during deficiency, whereas n-9 fatty acids decreased. In the chicken brain the alterations were delayed and less distinct. The cerebellum phospholipids were rich in n-9 fatty acids and as a whole more saturated in comparison with the cerebrum. Cerebellar unsaturation increased when linolenic or linoleic acid was given. However, NE-producing dietary conditions were not accompanied by specific alterations in cerebellar phospholipid fatty acids due to the alpha-tocopherol content of the diet. Rather the alterations of membrane fatty acids in the liver seem to play a role in the pathogenesis of NE.

A panencephalopathic type of Creutzfeldt-Jakob disease with selective lesions of the thalamic nuclei in 2 Swiss patients.

Creutzfeldt-Jakob disease (CJD), a subacute spongiform encephalopathy, is generally included among the group of human and animal diseases which is transmissible by a non-conventional agent, the prion, whose expression is conditioned by the host's genome. The process leading to neuropathological changes is still unknown. We report the neuropathological findings in 2 cases of the "panencephalopathic" variant of CJD, which is relatively common in Japan, but extremely rare in Europe and North America. When compared with the classical form this variant is characterized by a relatively long clinical course with persistent vegetative state and primary involvement of the white matter presenting in the form of demyelination and gemistocytic gliosis. The selective involvement of certain thalamic nuclei is a particular pathological feature in both our cases. There was practically complete neuronal loss with diffuse gliosis of the anteroventral (AV) and dorsomedial (DM) nuclei, while the neuronal loss in the pulvinar remained moderate: the other nuclei were apparently spared. A similar involvement of the thalamus has been reported in fatal familial insomnia, a recently described prion disease in which these lesions are predominant. A comparable distribution has also been observed in other degenerative neurological diseases such as Steele-Richardson-Olszewski disease, Alzheimer disease, and thalamic dementia (selective thalamic atrophy or with multisystemic degeneration). The AV and DM nuclei, commonly referred to as "limbic thalamus" represent phylogenetically the most recent thalamic structures and would appear to play an important role in the superior functions in man as memory, attention and awareness. In our cases thalamic lesions are selective, bilateral, and symmetric, not explained by Wallerian degeneration. These lesions may be due to the primary pathogenetic properties of the infectious agent. The rapid clinical evolution in a persistent vegetative state could be consequential to precocious and severe disfunction of the limbic thalamus.

[Tissue lipid peroxidation in nutritional encephalomalacia of broiler chickens]. / Zur Erfassung der Gewebs-Lipidperoxidation bei der Nutritiven Enzephalomalazie des Broilers.

The consequences of different dietary fats in combination with two vitamin E levels on peroxidative tissue damage of chicken brain and liver and its meaning for development of nutritional encephalomalacia (NE) were investigated. A feeding experiment was performed with 1-day-old chickens from hens on a vitamin-E-poor diet. The animals received a vitamin-E-deficient basic diet containing 10% fat, rich in either C18:3n3-, C18:2n6- or C18:1n9-fatty acids. The fat was given either fresh or oxidized (peroxidation number: 250) and 0 or 50 ppm alpha-tocopherylacetate was added. Typical symptoms of NE occurred mainly in those groups fed with n6-fatty acids beginning on day 7. In order to evaluate oxidative tissue damage, conjugated dienes, fluorescent pigments and TBA-reactive substances were determined in liver, cerebrum and cerebellum. Brain was examined histologically. In liver and cerebrum, the feeding of oxidized fats led to a 20% increase in conjugated dienes. Fluorescent pigments could be determined only in the brain tissues. However, feeding conditions had no effect, although autofluorescence was observed histologically in the affected animals. TBA-reactive substances were heightened in cerebrum (30%) and liver (130%) as a result of feeding linolenic acid. Vitamin E deficiency doubled TBA-reactive substances only in the liver. The parameters measured did not show intensified lipid peroxidation in the cerebellum of the animals fed the NE producing diet. Rather, the liver seems to be affected by the oxidative stress.

Ruminal microbial alterations associated with sulfide generation in steers with dietary sulfate-induced polioencephalomalacia.

Holstein steers were fed carbohydrate-rich, short-fiber basal diets with and without added sodium sulfate. Steers fed the high-sulfate diet developed the CNS disorder polioencephalomalacia (PEM). The onset of signs of PEM was associated with increased sulfide concentration in the rumen fluid. Over the course of the disease, anaerobic rumen bacteria were enumerated in roll tubes by use of the Hungate method Lo determine the effect of dietary sulfate on sulfate-reducing bacterial numbers. Media used included a general type for total counts and sulfate containing media with and without cysteine to assess sulfate-reducing bacteria. Changes in total and sulfate reducing bacterial numbers attributable to dietary sulfate content were not observed. The capacity to generate hydrogen sulfide from sulfate in fresh rumen fluid in vitro was substantially increased only after steers had been fed the high sulfate diet for 10 to 12 days, which coincided with the onset of signs of PEM. The low capacity for hydrogen sulfide production of rumen fluid taken at earlier times in the feeding period suggests that rumen microorganisms must adapt to higher dietary sulfate content before they are capable of generating potentially toxic concentrations of sulfide.

The influence of dietary fatty acids and vitamin E on plasma prostanoids and liver microsomal alkane production in broiler chickens with regard to nutritional encephalomalacia.

Nutritional encephalomalacia (NE) in broiler chicken is considered as a peroxidative dysfunction caused by vitamin E-deficient diets. A feeding experiment was performed to investigate the consequences of feeding different fats in combination with increasing amounts of vitamin E on liver lipid peroxidation and plasma prostanoid pattern. Newly hatched chicks from hens on a vitamin E-poor diet were fed with either mainly linolenic, linoleic or oleic acid-rich oils in a vitamin E-deficient (5 ppm) basic diet. The animals were supplemented with vitamin E on three levels (0, 20 or 120 ppm). On appearance of the first symptoms of NE after 8 days post-hatching, the animals were examined. Typical symptoms with a high incidence only occurred in the group fed linoleic acid and 5 ppm vitamin E. Plasma prostanoids and microsomal alkane production in liver as a measure of endogenous lipid peroxidation were determined. The dietary conditions affected plasma prostaglandin E2 and thromboxane A2, but not prostacyclin. However, it seems unlikely that the prostanoids are involved in the pathogenesis of NE. Liver lipid peroxidation increased in vitamin E deficiency. The level of alkanes depended on the type of fat supplied. The consequences of the different dietary fats in combination with vitamin E deficiency on peroxidative metabolism of broiler chickens are evident, indicating that a high level of oxidative stress is imposed by the linoleic acid-rich fat.

Chick nutritional encephalomalacia and prostanoid formation.

Nutritional encephalomalacia (NE) was induced in young chicks using a diet low in vitamin E and containing 8% ethyl esters derived from safflower oil fatty acids (S-E group). The same diet with added alpha-tocopheryl acetate (S+E) failed to produce the pathology, and chicks receiving aerated linseed oil--high in alpha-linolenic acid and low in alpha-tocopherol (L-E)--did not develop symptoms. Formation of metabolites from labeled arachidonic acid (AA) by thrombocytes was similar in the S+E and S-E groups, yielding thromboxane B2 (TXB2) and hydroxy fatty acids as the major products. Collagen-induced thrombocyte aggregation and TXB2 production were not significantly different in the S-E and S+E groups, but aggregation values and TXB2 synthesis were significantly less in the L-E group than in the ataxic S-E chicks. Prostaglandin E2 production by aortal rings was significantly influenced by the diet; S-E yielded the highest value and L-E the lowest. These results show that alpha-linolenic acid causes alterations in the AA metabolism and thrombocyte function in young chicks.

Clinical and biochemical alterations in calves with nutritionally induced polioencephalomalacia.

Polioencephalomalacia (PEM) was induced in calves by feeding a semipurified, low-roughage diet of variable copper and molybdenum composition. Two formulations resulting in Cu-insufficient and Cu-sufficient forms of the diet were fed (n = 10 and 4 calves, respectively); both diets induced PEM. Clinical signs of disease developed as early as 15 days after transition to the experimental diets and included impaired vision, decreased response to external stimuli, and abnormal gait. Grossly evident cerebrocortical lesions consisted of laminar areas of cavitation and/or autofluorescence seen under UV illumination. Hepatic Cu concentration was decreased in calves fed the Cu-insufficient diet, but not below normal range. During the course of feeding either diet, rumen pH decreased, rumen volatile fatty acid concentrations increased, rumen and blood lactic acid concentrations increased, and rumen and plasma thiamine concentrations increased. The thiamine pyrophosphate effect on erythrocyte transketolase activity was unaltered in calves of either diet group. This nutritionally induced form of PEM does not appear to be related to Cu deficiency or reduction in plasma or rumen thiamine concentration.

Nutritional encephalomalacia in the chick: an exposure of the vulnerable period for cerebellar development and the possible need for both omega 6- and omega 3-fatty acids.

1. Cockerels (1-d-old) received over a period of 4 weeks, a balanced diet containing either safflower oil (diet S) or linseed oil (diet L) as a source of polyunsaturated fatty acids (PUFA). Body-weight, and weights of cerebrum and cerebellum increased at similar rates in the two dietary groups. The total fatty acids (FA) of the cerebellum differed from the cerebral FA by their higher PUFA and oleic acid contents and their lower stearic acid level. During the 3rd week of life there was a spurt in accretion of PUFA in the cerebellum, but not in the cerebrum. At the end of the experimental period phosphatidylethanolamine was present at twice the concentration in the cerebellum, compared with the cerebrum. 2. Diets S and L resulted in extensive mutual replacement of omega 6- and omega 3-FA in brain, without any significant change in the total PUFA. Brain oleic acid concentration was higher in the diet-L group than in the diet-S group, but saturated FA were not affected by the dietary treatments. 3. These results may be relevant to basic brain biology and to chick nutritional encephalomalacia (NE). This disease, which specifically affects the cerebellum and is readily induced by diets supplying linoleic acid but deficient in vitamin E, usually reaches its highest incidence during the 3rd week of life and may thus be related to the cerebellar PUFA spurt that occurs at that time. The fact that NE was induced by linoleic acid, while alpha-linolenic acid exerted a protective action, points to an overproduction of arachidonic-derived eicosanoids as a factor in the etiology of the cerebellar lesion and possibly a structural change due to a loss of docosahexaenoic acid and gain of arachidonic acid in the chicks given diet S.