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Saccadic Palsy following Cardiac Surgery: Possible Role of Perineuronal Nets.

Eggers SD, Horn AK, Roeber S, Härtig W, Nair G, Reich DS, Leigh RJ - PLoS ONE (2015)

Bottom Line: Excitatory burst neurons and omnipause neurons were preserved and still received synaptic input, but their surrounding PN showed severe loss or fragmentation.How a postulated hypoxic mechanism could selectively damage the PN remains unclear.We propose that the well-studied saccadic eye movement system provides an accessible model to evaluate the role of PN in health and disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota, United States of America.

ABSTRACT

Objective: Perineuronal nets (PN) form a specialized extracellular matrix around certain highly active neurons within the central nervous system and may help to stabilize synaptic contacts, promote local ion homeostasis, or play a protective role. Within the ocular motor system, excitatory burst neurons and omnipause neurons are highly active cells that generate rapid eye movements - saccades; both groups of neurons contain the calcium-binding protein parvalbumin and are ensheathed by PN. Experimental lesions of excitatory burst neurons and omnipause neurons cause slowing or complete loss of saccades. Selective palsy of saccades in humans is reported following cardiac surgery, but such cases have shown normal brainstem neuroimaging, with only one clinicopathological study that demonstrated paramedian pontine infarction. Our objective was to test the hypothesis that lesions of PN surrounding these brainstem saccade-related neurons may cause saccadic palsy.

Methods: Together with four controls we studied the brain of a patient who had developed a permanent selective saccadic palsy following cardiac surgery and died several years later. Sections of formalin-fixed paraffin-embedded brainstem blocks were applied to double-immunoperoxidase staining of parvalbumin and three different components of PN. Triple immunofluorescence labeling for all PN components served as internal controls. Combined immunostaining of parvalbumin and synaptophysin revealed the presence of synapses.

Results: Excitatory burst neurons and omnipause neurons were preserved and still received synaptic input, but their surrounding PN showed severe loss or fragmentation.

Interpretation: Our findings support current models and experimental studies of the brainstem saccade-generating neurons and indicate that damage to PN may permanently impair the function of these neurons that the PN ensheathe. How a postulated hypoxic mechanism could selectively damage the PN remains unclear. We propose that the well-studied saccadic eye movement system provides an accessible model to evaluate the role of PN in health and disease.

No MeSH data available.


Related in: MedlinePlus

Brainstem cutting planes and transverse sections.(A) Brainstem sagittal view demonstrating cutting planes. The blocks containing the rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF), the oculomotor nucleus (nIII), the paramedian pontine reticular formation (PPRF) including the excitatory (EBN) and inhibitory burst neurons (IBN), the nucleus raphe interpositus (RIP) containing omnipause neurons (OPN), and the abducens nucleus (nVI), were cut in series of 10μm and 5μm thick sections. (B) Caudal view of the block containing the RIMLF. (C) Caudal view of the block containing the PPRF and OPN region. Scale bar B,C = 1cm. INC, interstitial nucleus of Cajal; IO, inferior olive; MB, mammillary body; LGN, lateral geniculate nucleus; MCP, medial cerebellar peduncle; MGN, medial geniculate nucleus; MT, mammillothalamic tract; nIV, trochlear nucleus; NVI, abducens nerve; PC, posterior commissure; RN, red nucleus; TR, tractus retroflexus; PC, posterior commissure; PUL, pulvinar; SC, superior colliculus; SCP, superior cerebellar peduncle; SN, substantia nigra.
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pone.0132075.g001: Brainstem cutting planes and transverse sections.(A) Brainstem sagittal view demonstrating cutting planes. The blocks containing the rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF), the oculomotor nucleus (nIII), the paramedian pontine reticular formation (PPRF) including the excitatory (EBN) and inhibitory burst neurons (IBN), the nucleus raphe interpositus (RIP) containing omnipause neurons (OPN), and the abducens nucleus (nVI), were cut in series of 10μm and 5μm thick sections. (B) Caudal view of the block containing the RIMLF. (C) Caudal view of the block containing the PPRF and OPN region. Scale bar B,C = 1cm. INC, interstitial nucleus of Cajal; IO, inferior olive; MB, mammillary body; LGN, lateral geniculate nucleus; MCP, medial cerebellar peduncle; MGN, medial geniculate nucleus; MT, mammillothalamic tract; nIV, trochlear nucleus; NVI, abducens nerve; PC, posterior commissure; RN, red nucleus; TR, tractus retroflexus; PC, posterior commissure; PUL, pulvinar; SC, superior colliculus; SCP, superior cerebellar peduncle; SN, substantia nigra.

Mentions: The whole brain was collected the day of death and fixed in 10% formalin for 2 weeks. Next, the brain was suspended in Fomblin (Solvay Solexis, West Deptford, NJ) for ex vivo 7 tesla MRI, as previously described [27]. After refixation in formalin, the brain was dissected, and the brainstem was cut transversely into several 2cm thick slices, which were embedded in paraffin. The blocks containing the RIMLF, the oculomotor nucleus, the PPRF including EBN and OPN, the abducens nucleus, and the IBN were cut in series of 10μm and 5μm thick sections (Fig 1A–1C). For neuropathological analysis, sections of each area were deparaffinized and stained with hematoxylin & eosin, cresyl violet and Luxol fast blue periodic acid-Schiff (LFB-PAS; myelin staining) using standard techniques. Immunocytochemical staining with polyclonal rabbit anti- glial fibrillary acid protein (GFAP, 1:3000, Dakocytomation; Glostrup, Denmark; N1506, RRID:AB_10013482) and mouse monoclonal anti-human HLA-DP, DQ, DR-antigen (clone CR3/43 1:100, Dakocytomation; Glostrup, Denmark; F081701, RRID: AB_578680) was performed to reveal reactive gliosis and activated microglia, respectively.


Saccadic Palsy following Cardiac Surgery: Possible Role of Perineuronal Nets.

Eggers SD, Horn AK, Roeber S, Härtig W, Nair G, Reich DS, Leigh RJ - PLoS ONE (2015)

Brainstem cutting planes and transverse sections.(A) Brainstem sagittal view demonstrating cutting planes. The blocks containing the rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF), the oculomotor nucleus (nIII), the paramedian pontine reticular formation (PPRF) including the excitatory (EBN) and inhibitory burst neurons (IBN), the nucleus raphe interpositus (RIP) containing omnipause neurons (OPN), and the abducens nucleus (nVI), were cut in series of 10μm and 5μm thick sections. (B) Caudal view of the block containing the RIMLF. (C) Caudal view of the block containing the PPRF and OPN region. Scale bar B,C = 1cm. INC, interstitial nucleus of Cajal; IO, inferior olive; MB, mammillary body; LGN, lateral geniculate nucleus; MCP, medial cerebellar peduncle; MGN, medial geniculate nucleus; MT, mammillothalamic tract; nIV, trochlear nucleus; NVI, abducens nerve; PC, posterior commissure; RN, red nucleus; TR, tractus retroflexus; PC, posterior commissure; PUL, pulvinar; SC, superior colliculus; SCP, superior cerebellar peduncle; SN, substantia nigra.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4489868&req=5

pone.0132075.g001: Brainstem cutting planes and transverse sections.(A) Brainstem sagittal view demonstrating cutting planes. The blocks containing the rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF), the oculomotor nucleus (nIII), the paramedian pontine reticular formation (PPRF) including the excitatory (EBN) and inhibitory burst neurons (IBN), the nucleus raphe interpositus (RIP) containing omnipause neurons (OPN), and the abducens nucleus (nVI), were cut in series of 10μm and 5μm thick sections. (B) Caudal view of the block containing the RIMLF. (C) Caudal view of the block containing the PPRF and OPN region. Scale bar B,C = 1cm. INC, interstitial nucleus of Cajal; IO, inferior olive; MB, mammillary body; LGN, lateral geniculate nucleus; MCP, medial cerebellar peduncle; MGN, medial geniculate nucleus; MT, mammillothalamic tract; nIV, trochlear nucleus; NVI, abducens nerve; PC, posterior commissure; RN, red nucleus; TR, tractus retroflexus; PC, posterior commissure; PUL, pulvinar; SC, superior colliculus; SCP, superior cerebellar peduncle; SN, substantia nigra.
Mentions: The whole brain was collected the day of death and fixed in 10% formalin for 2 weeks. Next, the brain was suspended in Fomblin (Solvay Solexis, West Deptford, NJ) for ex vivo 7 tesla MRI, as previously described [27]. After refixation in formalin, the brain was dissected, and the brainstem was cut transversely into several 2cm thick slices, which were embedded in paraffin. The blocks containing the RIMLF, the oculomotor nucleus, the PPRF including EBN and OPN, the abducens nucleus, and the IBN were cut in series of 10μm and 5μm thick sections (Fig 1A–1C). For neuropathological analysis, sections of each area were deparaffinized and stained with hematoxylin & eosin, cresyl violet and Luxol fast blue periodic acid-Schiff (LFB-PAS; myelin staining) using standard techniques. Immunocytochemical staining with polyclonal rabbit anti- glial fibrillary acid protein (GFAP, 1:3000, Dakocytomation; Glostrup, Denmark; N1506, RRID:AB_10013482) and mouse monoclonal anti-human HLA-DP, DQ, DR-antigen (clone CR3/43 1:100, Dakocytomation; Glostrup, Denmark; F081701, RRID: AB_578680) was performed to reveal reactive gliosis and activated microglia, respectively.

Bottom Line: Excitatory burst neurons and omnipause neurons were preserved and still received synaptic input, but their surrounding PN showed severe loss or fragmentation.How a postulated hypoxic mechanism could selectively damage the PN remains unclear.We propose that the well-studied saccadic eye movement system provides an accessible model to evaluate the role of PN in health and disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota, United States of America.

ABSTRACT

Objective: Perineuronal nets (PN) form a specialized extracellular matrix around certain highly active neurons within the central nervous system and may help to stabilize synaptic contacts, promote local ion homeostasis, or play a protective role. Within the ocular motor system, excitatory burst neurons and omnipause neurons are highly active cells that generate rapid eye movements - saccades; both groups of neurons contain the calcium-binding protein parvalbumin and are ensheathed by PN. Experimental lesions of excitatory burst neurons and omnipause neurons cause slowing or complete loss of saccades. Selective palsy of saccades in humans is reported following cardiac surgery, but such cases have shown normal brainstem neuroimaging, with only one clinicopathological study that demonstrated paramedian pontine infarction. Our objective was to test the hypothesis that lesions of PN surrounding these brainstem saccade-related neurons may cause saccadic palsy.

Methods: Together with four controls we studied the brain of a patient who had developed a permanent selective saccadic palsy following cardiac surgery and died several years later. Sections of formalin-fixed paraffin-embedded brainstem blocks were applied to double-immunoperoxidase staining of parvalbumin and three different components of PN. Triple immunofluorescence labeling for all PN components served as internal controls. Combined immunostaining of parvalbumin and synaptophysin revealed the presence of synapses.

Results: Excitatory burst neurons and omnipause neurons were preserved and still received synaptic input, but their surrounding PN showed severe loss or fragmentation.

Interpretation: Our findings support current models and experimental studies of the brainstem saccade-generating neurons and indicate that damage to PN may permanently impair the function of these neurons that the PN ensheathe. How a postulated hypoxic mechanism could selectively damage the PN remains unclear. We propose that the well-studied saccadic eye movement system provides an accessible model to evaluate the role of PN in health and disease.

No MeSH data available.


Related in: MedlinePlus