Cellular and Molecular Biology of Autism Spectrum Disorders

Immunoexcitotoxicity as a Central Mechanism of Autism Spectrum Disorders

Author(s): Russell L. Blaylock

Pp: 47-72 (26)

DOI: 10.2174/978160805196011001010047

* (Excluding Mailing and Handling)

Abstract

Autism has undergone a tremendous amount of study, and a number of often seemingly unconnected disorders have been disclosed. Yet, despite an enormous amount of study, no central mechanism to explain the causation of this syndrome or why it affects only a subset of children has come forth. In this chapter I propose such a central mechanism that explains a great number of biochemical, histological, neurodevelopmental and systemic dysfunctions, as well as behavioral findings in autism spectrum disorders (ASD). Since the discovery of excitotoxicity by Olney in 1968, neuroscientists have determined that not only is glutamate a neurotransmitter, but it is the most abundant neurotransmitter in the brain, exceeding the more traditional neurotransmitters combined. Recent studies have also shown that glutamatergic receptors (GluRs) interact with other receptors, not only neurotransmitters, but also immune receptors, in a way that can alter their sensitivity. Chronic brain inflammation is known to dramatically enhance the sensitivity of N-methyl-D-aspartic acid (NMDA) and α- amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) type GluRs and interfere with glutamate removal from the extraneuronal space, where it can trigger excitotoxicity and abnormal synaptic and dendritic physiology over a prolonged period. Importantly, neuroscience studies have clearly shown that sequential systemic immune stimulation can not only activate the brain ’ s immune system, microglia and astrocytes, but that there occurs an amplified response to both subsequent stimulation, either systemic or within the CNS. The ASD child is exposed to such sequential immune stimulation via a growing number of vaccines, recurrent infections, chemical toxins and persistent viral infections.

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      • 11. app/Models/ContentAccess.php:647
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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314566045 and j.to_ip >=314566045 )) and ((j.from_date <= 1739834570 and j.to_date >= 1739834570 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1576) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314566045 and j.to_ip >=314566045 )) and ((j.from_date <= 1739834570 and j.to_date >= 1739834570 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1576) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 314566045 and j.to_ip >=314566045 )) and ((j.from_date <= 1739834570 and j.to_date >= 1739834570 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 1576)
      600μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 905 and `b`.`banner_from_date` <= 1739834570 and `b`.`banner_to_date` >= 1739834570 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.04msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 905
      • 3: 1739834570
      • 4: 1739834570
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='90b64d15be6e0f00e4f3963fa4044365'
      220μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        pfsv2CwQ0j2fymV2aQbNF4q9mXcWQC6b1YiTHupN
        uc_cart_id
        90b64d15be6e0f00e4f3963fa4044365
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/1576" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/1576
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:16 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Mon, 17 Feb 2025 23:22:50 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6ImNTYnNqV2c4M0o0ZVc5a0plcXZYNVE9PSIsInZhbHVlIjoiaUpYNkpJb0F6WGxja28vU2RKVjNRbUQ1Tkl3TmNobnRBdnJsS0QweXJFMVN2S0V3Z29idFd1cm9pV1k2Z3FHU3UwTXNjVmhsWFlzbmkreWVWVThKVjBwR1gwTGV2N3NuT2h6WENxNjd4TGxhRnFIOXZoa0pvbjZPOXZwd3NQZWwiLCJtYWMiOiI2YmVmYTFkYjI2YTE1YTkyMTVlOTM5MjA3OGQyYTFjYjRiNWQ2NzhhOTYxM2FmOTA3NTM1Njk4OTFkN2VkZDM3IiwidGFnIjoiIn0%3D; expires=Thu, 20 Feb 2025 11:22:50 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6ImNTYnNqV2c4M0o0ZVc5a0plcXZYNVE9PSIsInZhbHVlIjoiaUpYNkpJb0F6WGxja28vU2RKVjNRbUQ1Tkl3TmNobnRBdnJsS0QweXJFMVN2S0V3Z29idFd1cm9pV1k2Z3FHU3UwTXNjV" 1 => "alphaeurekaselectnet_session=eyJpdiI6IjdwYzVtbURONTFpdGxPa0REdzVwWEE9PSIsInZhbHVlIjoidlRzMHlDdlAzUnVWRmFCU0s4TlAxNDFSTllWR2U0S1RoaGpUNlVXQlVDSEJJaW5QdXpCNkIrMy9JRzE5QlNHSFpYMXlqQXRlOGtVeER0cG43U0Q3dmFBdzdLR29WMEFjS3kyaTNNbitlUHpmK2lNVmhHYnN0MVFVQmdDdEh2OUQiLCJtYWMiOiJiMThkMmM3YTU1ODQ5ZGI0OGNmMzM0MjllMmQ3MTE3YWJiZWVlYWRmNmZmNmU1NmMxYzVkYmVjMjQ3NWM5Y2ViIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IjdwYzVtbURONTFpdGxPa0REdzVwWEE9PSIsInZhbHVlIjoidlRzMHlDdlAzUnVWRmFCU0s4TlAxNDFSTllWR2U0S1RoaGpUNlVXQlVDSEJJaW5QdXpCNkIrMy9" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6ImNTYnNqV2c4M0o0ZVc5a0plcXZYNVE9PSIsInZhbHVlIjoiaUpYNkpJb0F6WGxja28vU2RKVjNRbUQ1Tkl3TmNobnRBdnJsS0QweXJFMVN2S0V3Z29idFd1cm9pV1k2Z3FHU3UwTXNjVmhsWFlzbmkreWVWVThKVjBwR1gwTGV2N3NuT2h6WENxNjd4TGxhRnFIOXZoa0pvbjZPOXZwd3NQZWwiLCJtYWMiOiI2YmVmYTFkYjI2YTE1YTkyMTVlOTM5MjA3OGQyYTFjYjRiNWQ2NzhhOTYxM2FmOTA3NTM1Njk4OTFkN2VkZDM3IiwidGFnIjoiIn0%3D; expires=Thu, 20-Feb-2025 11:22:50 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6ImNTYnNqV2c4M0o0ZVc5a0plcXZYNVE9PSIsInZhbHVlIjoiaUpYNkpJb0F6WGxja28vU2RKVjNRbUQ1Tkl3TmNobnRBdnJsS0QweXJFMVN2S0V3Z29idFd1cm9pV1k2Z3FHU3UwTXNjV" 1 => "alphaeurekaselectnet_session=eyJpdiI6IjdwYzVtbURONTFpdGxPa0REdzVwWEE9PSIsInZhbHVlIjoidlRzMHlDdlAzUnVWRmFCU0s4TlAxNDFSTllWR2U0S1RoaGpUNlVXQlVDSEJJaW5QdXpCNkIrMy9JRzE5QlNHSFpYMXlqQXRlOGtVeER0cG43U0Q3dmFBdzdLR29WMEFjS3kyaTNNbitlUHpmK2lNVmhHYnN0MVFVQmdDdEh2OUQiLCJtYWMiOiJiMThkMmM3YTU1ODQ5ZGI0OGNmMzM0MjllMmQ3MTE3YWJiZWVlYWRmNmZmNmU1NmMxYzVkYmVjMjQ3NWM5Y2ViIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IjdwYzVtbURONTFpdGxPa0REdzVwWEE9PSIsInZhbHVlIjoidlRzMHlDdlAzUnVWRmFCU0s4TlAxNDFSTllWR2U0S1RoaGpUNlVXQlVDSEJJaW5QdXpCNkIrMy9" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "pfsv2CwQ0j2fymV2aQbNF4q9mXcWQC6b1YiTHupN" "uc_cart_id" => "90b64d15be6e0f00e4f3963fa4044365" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/1576" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:22:50GET/chapter/1576112192