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Despite bilateral hippocampal damage dating to the perinatal or early childhood period and severely impaired episodic memory, patients with developmental amnesia continue to exhibit well‐developed semantic memory across the developmental trajectory. Detailed information on the extent and focality of brain damage in these patients is needed to hypothesize about the neural substrate that supports their remarkable capacity for encoding and retrieval of semantic memory. In particular, we need to assess whether the residual hippocampal tissue is involved in this preservation, or whether the surrounding cortical areas reorganize to rescue aspects of these critical cognitive memory processes after early injury. We used voxel‐based morphometry (VBM) analysis, automatic (FreeSurfer) and manual segmentation to characterize structural changes in the brain of an exceptionally large cohort of 23 patients with developmental amnesia in comparison with 32 control subjects. Both the VBM and the FreeSurfer analyses revealed severe structural alterations in the hippocampus and thalamus of patients with developmental amnesia. Milder damage was found in the amygdala, caudate, and parahippocampal gyrus. Manual segmentation demonstrated differences in the degree of atrophy of the hippocampal subregions in patients. The level of atrophy in CA‐DG subregions and subicular complex was more than 40%, while the atrophy of the uncus was moderate (−24%). Anatomo‐functional correlations were observed between the volumes of residual hippocampal subregions in patients and selective aspects of their cognitive performance, viz, intelligence, working memory, and verbal and visuospatial recall. Our findings suggest that in patients with developmental amnesia, cognitive processing is compromised as a function of the extent of atrophy in hippocampal subregions. More severe hippocampal damage may be more likely to promote structural and/or functional reorganization in areas connected to the hippocampus. In this hypothesis, different levels of hippocampal function may be rescued following this variable reorganization. Our findings document not only the extent, but also the limits of circuit reorganization occurring in the young brain after early bilateral hippocampal damage. [ABSTRACT FROM AUTHOR]

The cover image is based on the article Anatomo‐functional changes in neural substrates of cognitive memory in developmental amnesia: Insights from automated and manual Magnetic Resonance Imaging examinations by Loïc J. Chareyron et al., https://doi.org/10.1002/hipo.23638..By Loïc J. Chareyron; W. K. Kling Chong; Tina Banks; Neil Burgess; Richard C. Saunders and Faraneh Vargha‐KhademReported by Author; Author; Author; Author; Author; Author [Extracted from the article]

PPARs are ligand-dependent nuclear transcription factors that regulate β oxidation of fatty acids in various tissues. PPARα ligands are also known to protect against pathological damage especially resulting from angiotensin II (AII) hypertension. However, the role of PPARα in regulation of hemodynamics under physiological conditions is not fully known. In this study, we evaluated the modulation by PPARα of the renal and systemic hemodynamic effects of All. Clofibrate (250 mg/kg), fenofibrate (100 mg/kg), or WY14643 (45 mg/kg), PPARα ligands, each elicited a 3-4-fold increase in renal peroxisomal β-oxidation that was accompanied by increased renal NO production - 92±7, 73±5, or 59±6%, respectively. Clofibrate blunted AII (3-100 ng/kg)-induced increase in mean arterial blood pressure (MABP; 46±6%, p<0.05) and the reduction in renal cortical blood flow (CBF, laser Doppler flowmetry, 29±4%, p<0.05). L-NAME but not D-NAME (100 mg/L) attenuated clofibrate-induced inhibition of AII responses. In the presence of losartan (5 mg/kg), clofibrate uncovered a hypotensive effect of All and further blunted the residual renal vasoconstriction. L-NAME but not D-NAME blunted the effects of losartan and blocked the hypotensive effects of All in losartan-treated rats. Except for WY14643, AT1-receptor expression was down regulated (44±6%) while AT2 receptor expression was upregulated (6-fold, p<0.05) in whole kidney homogenates from rats treated with PPARα ligands. These data suggest that PPARα activation counters AT1-mediated pressor and vasoconstrictor effects and that during AT1 receptor blockade, PPARα activation leads to hypotension that is coupled to AT2 receptor activation by a mechanism probably involving NO production. [ABSTRACT FROM AUTHOR]

Despite bilateral hippocampal damage dating to perinatal or early-childhood period, and severely-impaired episodic memory that unfolds in later childhood, patients with developmental amnesia continue to exhibit well-developed semantic memory across the developmental trajectory. Detailed information on the extent and focality of brain damage in these patients is needed to hypothesize about the neural substrate that supports their remarkable capacity for encoding and retrieval of semantic memory. In particular, we need to assess whether the residual hippocampal tissue is involved in this preservation, or whether the surrounding cortical areas reorganise to rescue aspects of these critical cognitive memory processes after early injury. We used voxel-based morphometry (VBM) analysis, automatic (FreeSurfer) and manual segmentation to characterize structural changes in the brain of an exceptionally large cohort of 23 patients with developmental amnesia in comparison with 32 control subjects. Both the VBM and the FreeSurfer analyses revealed severe structural alterations in the hippocampus and thalamus of patients with developmental amnesia. Milder damage was found in the amygdala, caudate and parahippocampal gyrus. Manual segmentation demonstrated differences in the degree of atrophy of the hippocampal subregions in patients. The level of atrophy in CA-DG subregions and subicular complex was more than 40% while the atrophy of the uncus was moderate (-23%). Anatomo-functional correlations were observed between the volumes of residual hippocampal subregions in patients and selective aspects of their cognitive performance viz, intelligence, working memory, and verbal and visuospatial recall. Our findings suggest that in patients with developmental amnesia, cognitive processing is compromised as a function of the extent of atrophy in hippocampal subregions, such that the greater the damage, the more likely it is that surrounding cortical areas will be recruited to rescue the putative functions of the damaged subregions. Our findings document for the first time not only the extent, but also the limits of circuit reorganization occurring in the young brain after early bilateral hippocampal damage.

Background: Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent nuclear transcription factors that regulate beta-oxidation of fatty acids in various tissues. PPARalpha ligands also protect against pathological damage especially resulting from angiotensin II hypertension. The modulating effect of PPARalpha on hemodynamic effects elicited by angiotensin II under normal conditions, however, is not fully known., Method: We therefore evaluated renal and systemic hemodynamic effects of angiotensin II in normal animals treated with PPARalpha ligands., Results: PPARalpha ligands clofibrate (250 mg/kg), fenofibrate (100 mg/kg), or pirixinic acid (WY14643; 45 mg/kg) each elicited an increase in renal peroxisomal beta-oxidation, accompanied by increased renal nitric oxide production. Clofibrate blunted the angiotensin II (3-100 ng/kg)-induced increase in mean arterial blood pressure (P < 0.05) but attenuated the reduction in renal cortical blood flow (laser Doppler flowmetry; P < 0.05). N(omega)-nitro-L-arginine methyl ester (L-NAME) but not D-NAME (100 mg/l) blunted clofibrate-induced inhibition of angiotensin II responses. In the presence of the angiotensin type 1 (AT1)-antagonist losartan (3 mg/kg), clofibrate uncovered a hypotensive effect of angiotensin II and further blunted the residual renal vasoconstriction. L-NAME or the angiotensin type 2 (AT2)-antagonist (S-[+]-1-[(4-dimethylamino]-3-methylphenyl)methyl]-5-[diphenylacetyl]-4,5,6,7-tetrahydro-1H-imidazol[4,5-c]pyridine-6-carboxilic acid; PD123319), but not D-NAME, blunted the effects of losartan and blocked the hypotensive effects of angiotensin II in losartan-treated rats. Except in rats treated for 7 days with WY14643, AT1-receptor expression was downregulated (P < 0.05) while AT2-receptor expression was upregulated (P < 0.05) in renal cortical homogenates from rats treated with clofibrate or WY14643., Conclusion: These data suggest that PPARalpha activation counters AT1-mediated pressor and vasoconstrictor effects and that, during AT1 receptor blockade, PPARalpha activation leads to hypotension coupled to AT2-receptor activation by a mechanism probably involving nitric oxide production.